DIAGNOSTIC STRATEGY

The diagnostic strategy of Latin-SEQ uses an algorithm guided by the clinical suspicion of each patient as determined by the referring centre. Patients with hereditary neuromuscular diseases (NMDs) will be evaluated through specific genetic screening using Multiple Ligation Probe Amplification (MLPA) to rule out conditions such as Spinal Muscular Atrophy (SMA), Duchenne/Becker muscular dystrophy, and Charcot-Marie-Tooth neuropathies, or sequencing of recurrent mutations associated with congenital myasthenic syndromes and mitochondrial myopathies. This initial screening is expected to diagnose approximately 20% of cases. Cases not diagnosed through this method will proceed to whole exome sequencing.

In the first stage, exomes will be analysed focusing on a panel of over 600 genes related to neuromuscular diseases (based on http://www.musclegenetable.fr/) which will be updated every 6 months. This approach is expected to resolve 40-60% of cases. For unresolved cases, a more thorough analysis of the whole exome will be conducted, including sequencing of family members when possible. This approach will not only facilitate the diagnosis of rare diseases but also the identification of new genes. In such cases, studies will be conducted to validate the pathogenicity of identified variants and confirm their relevance using various criteria, including in silico analyses and functional studies in cellular or animal models.

In Latin-SEQ, the interpretation and analysis of genetic results follow a meticulous and rigorous process: the obtained data are analysed iteratively, and preliminary results are shared with referring physicians. These results are discussed in regular meetings to evaluate the findings based on the patient’s and family’s clinical presentation. For cases considered resolved, a final genetic report will be issued. For more complex cases, multidisciplinary meetings will be held where genetic results will be discussed alongside other available studies such as MRI or muscle biopsy.

GENETIC REPORTS

The genetic reports* issued by the coordinating team will provide information on the identified genetic variants and their classification according to the ACMG (American College of Medical Genetics and Genomics) guidelines, detailing each parameter included as well as relevant publications.

In genetic reports, the contact details of available PATIENT REGISTRIES/ASSOCIATIONS will be provided to the referring doctors, preferably within the country of origin or internationally, so they can share them with patients and their families in accordance with their protocols.

Unfortunately, the vast majority of NMDs have no cure or treatment; if any do, this information will also be included in the genetic reports. Clinical follow-up of patients is managed by the referring physicians.

*It is important to note that the results presented in these reports are obtained as part of a research study and therefore do not constitute a diagnostic credential. The interpretation and application of these data are the sole responsibility of the referring physicians. The Latin-SEQ team is not responsible for the use of the information contained in these reports.

*Please note that the analysis and interpretation provided in these reports depend on the correct identification of the samples and the accuracy of the clinical information provided.

Interpretation of Genetic Reports
POSITIVE:
LP/P variant(s) in a gene compatible with the phenotype
a) Heterozygous variant in an AD gene
b) Homozygous or compound heterozygous variants in an AR gene
COMPATIBLE:
a) Variant(s) of uncertain significance in a gene highly compatible with the phenotype
b) One heterozygous LP/P variant in an AR gene
INCONCLUSIVE:
Variant(s) of uncertain significance
(*) May change in the future
INCOMPATIBLE:
LP/P variant in a gene that is not compatible with the patient's phenotype
NEGATIVE:
No significant variants identified
(*) Study limitations
(**) May change in the future

LP/P: Likely Pathogenic/Pathogenic; AR: Autosomal Recessive; AD: Autosomal Dominant

Recurrent Variant Methodology

WES Methodology

  • 1

    Assay Method: Whole Exome Sequencing (WES), using the KAPA HyperExome capture kit (Roche) and the Illumina NovaSeq 6000 platform.

  • 2

    Bioinformatics Pipeline: Sequencing read mapping and identification of SNV/indel and CNV/SV variants are performed using DRAGEN v4.4.6. The resulting VCF files are annotated using VEP, SnpEff, SnpSift and InterVar for SNVs/indels, and AnnotSV for CNVs/SVs.

  • 3

    Data Analysis: The VCF files are uploaded to the Genome-Phenome Analysis Platform, GPAP, RD-Connect: https://platform.rd-connect.eu/#/

    Different filtering criteria are applied within the platform to identify potential disease-causing variants.

    During the primary analysis round, standard criteria commonly used for the genetic analysis of rare diseases are applied. These include a Minor Allele Frequency (MAF) of <1% in the control population, based on gnomAD v4.0, and a moderate or high Variant Effect Predictor (VEP) impact. This includes non-synonymous variants and in-frame indels, as well as truncating variants, such as nonsense variants, splice variants and frameshift indels.

    These criteria are assessed under different modes of inheritance, including recessive, dominant and X-linked inheritance. Single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy-number variants (CNVs) are analysed within the coding regions of the in silico panel applied.

    At this stage, the primary analysis panel is used, which contains 891 genes associated with NMDs. The complete list of genes is provided under PRIMARY GENE LIST.

    Where the initial analysis does not identify any relevant variants, a second round of analysis may be undertaken, guided by the patient’s phenotype.

    During this phase, expanded gene panels are applied according to the initial clinical suspicion and the discussions held during multidisciplinary meetings with the referring centre. This analysis may also include variants with a lower predicted impact, such as synonymous and intronic variants.

    Details of the secondary analysis performed for each patient are available upon request.

Segregation Methodology

  • 1

    Assay Method: PCR amplification and Sanger sequencing of variants of interest identified in the index case, using primers specific to each genomic region analysed.

  • 2

    Segregation Analysis: Variants are analysed in DNA samples from available relatives, both affected and unaffected, to determine their inheritance pattern and assess their co-segregation with the phenotype observed within the family.

    This analysis can also be used to establish the phase of compound heterozygous variants, determining whether they are located on different alleles, in trans, or on the same allele, in cis.

    The classification of a variant as de novo assumes that the stated biological relationships are correct, unless these relationships have been confirmed through other specific investigations.

The results are interpreted together with the family history, the expected mode of inheritance and the clinical information available.
Information on the primers used and the technical assay conditions is available upon request.

ACMG Classification

The genomic variants identified are classified in accordance with the original recommendations and pathogenicity criteria of the American College of Medical Genetics and Genomics, ACMG, Richards et al. 2015, as described under PATHOGENICITY EVIDENCE CRITERIA through freely available tools InterVar (https://wintervar.wglab.org/), Varsome (https://sso.varsome.com) and Franklin (https://franklin.genoox.com). Additional genetic and clinical information is manually curated.

The report also indicates whether the identified variant has previously been reported in the scientific literature or in clinical databases  (ClinVar and LOVD https://www.lovd.nl/). Please note that this information and the resulting classification may be subject to change, as described under LIMITATIONS.

Pathogenicity Evidence Criteria

  • Pathogenic Very Strong:

    • PVS1: Applied to protein-truncating variants, including nonsense, frameshift or splice variants, in genes where loss of function is an established disease mechanism.

  • Pathogenic Strong (PS):

    • PS1: The same amino acid change as a previously established pathogenic variant, but resulting from a different nucleotide change.
    • PS2: A confirmed de novo variant in the patient, with confirmation of both maternity and paternity.
    • PS3: Functional studies demonstrate a damaging effect consistent with the disease mechanism.
    • PS4: The variant is significantly more frequent in affected individuals than in unaffected individuals or controls.

  • Pathogenic Moderate (PM):

    • PM1: The variant is located within a functionally relevant region or mutational hot spot.
    • PM2: The variant is absent or present at a very low frequency in the control population, such as gnomAD.
    • PM3: In recessive disorders, the variant is detected in trans with another pathogenic variant.
    • PM4: The variant alters the length of the protein, such as an in-frame indel or stop-loss variant, in a gene where this is an established disease-causing mechanism.
    • PM5: A novel amino acid change affecting a residue where a different pathogenic alteration has previously been identified..
    • PM6: The variant is assumed to be de novo, without parental confirmation.

  • Pathogenic Supporting (PP):

    • PP1: Co-segregation with the disease in multiple affected relatives.
    • PP2: A missense variant in a gene with low tolerance to this type of variation and in which missense variants are an established cause of disease.
    • PP3: Multiple computational methods predict a deleterious effect, for example REVEL or CADD.
    • PP4: The patient’s clinical presentation and medical history are highly specific for the disease.
    • PP5: Previously reported by a reliable source. This criterion is considered obsolete by ClinGen and should be used with caution.

Limitations

The internal evaluation of the specificity and sensitivity of the variant-detection protocols using the Roche® KAPA HyperExome capture kit is 99.54% and 99.69%, respectively, for single-nucleotide variants, and 70.62% and 89.99%, respectively, for small insertions and deletions of up to 10 nucleotides.

Other types of genetic variants, such as repeat expansions, copy-number variants, structural variants or variants located in regions of high sequence homology, including pseudogenes and homologous regions, may not be detected.

This analysis also does not capture deep intronic variants, intergenic regions, or variants located within promoter or regulatory regions of a gene.

Consecutive variants forming haplotypes are not combined into multi-nucleotide variants (MNVs) and are reported as individual events.

Variants of uncertain significance (VUS) in genes that appear to be incompatible with the patient’s available clinical presentation are not included in the genetic reports, but may be provided upon request.

Variants identified during exome analysis are not systematically validated using an independent method. Where validation or an additional investigation is performed, this will be specified in the corresponding report.

Unless parental segregation studies are performed, the compound heterozygosity of variants and the biparental inheritance of homozygous variants are not confirmed and are only assumed.

In additional segregation studies performed using Sanger sequencing, the classification of a variant as de novo assumes that the stated biological relationships are correct, unless these relationships have been confirmed through other specific investigations.

Unless otherwise specified, each patient’s genomic data are analysed using an in silico panel of 891 genes associated with neuromuscular diseases. The complete list of genes included in this primary panel is provided under PRIMARY GENE LIST.

Genomic variants are classified according to the original recommendations of the American College of Medical Genetics and Genomics, ACMG, Richards et al. 2015.

Both the classification of variants and the interpretation of their diagnostic relevance are based on the scientific and clinical knowledge available at the time of analysis. They are therefore subject to change as new relevant information becomes available.

PRIMARY LIST OF GENES

This primary panel was created based on the most recent version of the Neuromuscular Gene Table (https://www.worldmusclesociety.org/page/gene-table) (Benarroch et al., 2025, https://pubmed.ncbi.nlm.nih.gov/41448968/). It has also been supplemented with information from public sources and unpublished internal data.

The list is reviewed approximately every six months.
Current version, July 2026, n=891:

AARS1, AARS2, ABCC9, ABCD3, ABHD16A, ABHD5, ABRA, ACAD9, ACADVL, ACTA1, ACTC1, ACTN2, ACTN3, ACVR1, ADAMTS15, ADCY6, ADGRG6, ADPRS, ADSS1, AFG3L2, AGL, AGRN, AHCY, AHNAK2, AIFM1, AKAP9, ALDH18A1, ALDH3A1, ALDH3A2, ALDOA, ALG14, ALG2, ALPK3, ALS2, AMFR, AMPD1, AMPD2, ANG, ANK2, ANKRD1, ANKRD2, ANKRD23, ANO10, ANO5, ANXA1, ANXA11, AP4B1, AP4E1, AP4M1, AP4S1, AP5Z1, APOBEC2, APOO, APTX, AR, ARHGAP19, ARHGEF10, ARL6IP1, ART1, ASAH1, ASB12, ASB2, ASB5, ASCC1, ASCC3, ATAD3A, ATG5, ATG7, ATL1, ATL3, ATM, ATP13A2, ATP1A1, ATP1A2, ATP1B4, ATP2A1, ATP2A2, ATP5F1B, ATP7A, ATXN1, ATXN10, ATXN2, ATXN3, ATXN7, ATXN8, ATXN8OS, B3GALNT2, B4GALNT1, B4GAT1, BAG3, BAG5, BEAN1, BEST3, BET1, BICD2, BIN1, BSCL2, C10orf71, C19orf12, C9orf72, CA3, CA8, CACNA1A, CACNA1C, CACNA1G, CACNA1H, CACNA1S, CACNB2, CACNB4, CACNG1, CACNG6, CADM3, CALM1, CALM2, CALM3, CALR3, CAP2, CAPN1, CAPN3, CAPNS1, CASQ1, CASQ2, CAV3, CAVIN1, CAVIN4, CCDC78, CCDC88C, CCT5, CDC40, CDH2, CELSR1, CFAP276, CFL2, CHAT, CHCHD10, CHD8, CHKB, CHMP2B, CHP1, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, CIAO1, CKM, CLCN1, CLN3, CLTCL1, CMYA5, CNBP, CNTN1, CNTNAP1, COA7, COL12A1, COL13A1, COL25A1, COL6A1, COL6A2, COL6A3, COLQ, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ9, COX15, COX16, COX18, COX20, COX6A1, COX6A2, CPT1C, CPT2, CRPPA, CRYAB, CSDE1, CSRP3, CTDP1, CTNNA3, CWF19L1, CYP2U1, CYP7B1, DAB1, DAG1, DARS2, DCAF8, DCTN1, DDHD1, DDHD2, DDIT4L, DES, DGAT2, DGUOK, DHTKD1, DMD, DMPK, DNA2, DNAJB2, DNAJB4, DNAJB6, DNM2, DNMT1, DOK7, DOLK, DPAGT1, DPM1, DPM2, DPM3, DSC2, DSG2, DSP, DST, DSTYK, DTNA, DUSP13B, DUSP29, DUX4, DYNC1H1, DYSF, ECEL1, EEF1A2, EEF2, EGF, EGR2, ELOVL4, ELOVL5, ELP1, EMD, EMILIN1, ENDOG, ENO3, ENTPD1, ENTPD5, ERBB3, ERBB4, ERLIN1, ERLIN2, ETFA, ETFB, ETFDH, EXOSC3, EXOSC8, EXOSC9, EYA4, FA2H, FABP3, FAM111B, FARS2, FASTKD2, FAT2, FBLN5, FBP2, FBXL4, FBXO32, FBXO38, FDX2, FEM1A, FGD4, FGF14, FHL1, FHL3, FHOD3, FICD, FIG4, FILIP1, FKRP, FKTN, FLAD1, FLII, FLNA, FLNC, FLVCR1, FOXK2, FTH1, FTL, FUS, FXN, FXR1, GAA, GAN, GAPDH, GARS1, GATAD1, GBA2, GBE1, GBF1, GDAP1, GDAP2, GFER, GFPT1, GGPS1, GIPC1, GJA5, GJB1, GJB3, GJC2, GLDN, GLE1, GLUL, GMPPB, GNB4, GNE, GOLGA2, GOSR2, GPD1L, GRID2, GRM1, GYG1, GYS1, H19, HACD1, HACE1, HARS1, HCN4, HEXB, HINT1, HJV, HK1, HMGCR, HMGCS1, HNRNPA1, HNRNPA2B1, HNRNPDL, HOXD10, HPDL, HRAS, HSP90AB1, HSPB1, HSPB3, HSPB6, HSPB7, HSPB8, HSPD1, HSPG2, IBA57, IDI2, IFRD1, IGFN1, IGHMBP2, ILK, INF2, INPP5K, IP6K3, ISCU, ITGA7, ITPR1, ITPR3, JAG1, JAG2, JPH1, JPH2, JSRP1, JUP, KARS1, KBTBD13, KCNA1, KCNA5, KCNA7, KCNC3, KCND3, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ11, KCNJ12, KCNJ18, KCNJ2, KCNJ5, KCNQ1, KIDINS220, KIF1A, KIF1B, KIF1C, KIF20A, KIF21A, KIF26B, KIF5A, KLC2, KLHL30, KLHL33, KLHL38, KLHL40, KLHL41, KLHL9, KPNA3, KY, L1CAM, LAMA2, LAMA4, LAMA5, LAMB2, LAMC1, LAMP2, LARGE1, LAS1L, LDB3, LDHA, LETM1, LIG3, LIMS2, LINGO4, LITAF, LMNA, LMOD2, LMOD3, LPCAT3, LPIN1, LRIF1, LRP10, LRP12, LRP4, LRRC38, LRSAM1, MACF1, MAFA, MAG, MAMDC2, MAP3K20, MAPT, MARS1, MARS2, MATR3, MB, MCM3AP, MCOLN1, MEGF10, MET, MFN2, MGME1, MIB1, MICU1, MIR1-1HG, MIR133A2, MKNK2, MLIP, MME, MORC2, MPDU1, MPV17, MPZ, MRE11, MRLN, MRPL3, MRPL44, MRPS25, MSTN, MSTO1, MT1X, MT2A, MT-CO1, MT-CO2, MT-CYB, MTHFSD, MTM1, MTMR2, MT-ND1, MTND1P23, MT-ND2, MTND2P28, MT-ND3, MT-ND4, MT-ND5, MT-ND6, MTO1, MTPAP, MTRFR, MT-RNR1, MT-RNR2, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY, MUSK, MYADML2, MYBPC1, MYBPC2, MYBPC3, MYBPH, MYF6, MYH1, MYH14, MYH2, MYH3, MYH6, MYH7, MYH8, MYL1, MYL11, MYL12A, MYL2, MYL3, MYL4, MYLK2, MYMK, MYMX, MYO18B, MYO9A, MYO9B, MYOD1, MYOG, MYOM3, MYOT, MYOZ1, MYOZ2, MYOZ3, MYPN, NAA10, NAGLU, NARS1, NBAS, NDRG1, NDUFAF1, NDUFB10, NEB, NEFH, NEFL, NEK1, NEK9, NEXN, NFU1, NGF, NHERF1, NIPA1, NKX6-2, NMNAT2, NOP56, NOTCH2NLC, NPPA, NPTX1, NRAP, NSUN3, NT5C2, NTRK1, NUP155, NUP88, NUTM2B-AS1, OBSCN, OGDHL, OPA1, OPTN, ORAI1, OXA1L, PABPN1, PACSIN3, PAX7, PCNA, PCYT2, PDK3, PDK4, PDLIM3, PDYN, PERM1, PEX7, PFKM, PFN1, PGAM2, PGK1, PGM1, PGPEP1L, PHKA1, PHKG1, PHOX2A, PHYH, PI4KA, PIEZO2, PIGK, PIP5K1C, PITRM1, PITX2, PKP2, PLD3, PLEC, PLEKHG5, PLIN4, PLN, PLP1, PMP2, PMP22, PMPCA, PNKP, PNPLA2, PNPLA6, PNPLA8, PNPT1, POC1A, POC1B, POC5, POGLUT1, POLG, POLG2, POLR3B, POMGNT1, POMGNT2, POMK, POMT1, POMT2, POPDC1, POPDC3, PPCS, PPDPFL, PPP1R27, PPP2R2B, PRDM12, PRDM16, PRDX3, PRECSIT, PREPL, PRKAG2, PRKAG3, PRKCG, PRPH, PRPS1, PRUNE1, PRX, PSAT1, PSEN1, PSEN2, PSMB4, PTPN11, PTRH2, PUM1, PURA, PUS1, PYGM, PYROXD1, RAB7A, RAF1, RAPSN, RBCK1, RBFOX1, RBM20, RBM7, REEP1, REEP2, RETREG1, RFC1, RFC4, RILPL1, RNASEH1, RNASEH1P1, RNF170, RNF216, RNF220, RNU4-2, RPH3A, RPL10, RPL18AP3, RPL19, RPL26, RPL27, RPL3L, RPLP0, RPLP1, RPLP2, RPS11, RPS12, RPS13, RPS16, RPS18, RRM2B, RTN2, RUBCN, RXYLT1, RYR1, RYR2, RYR3, SACS, SAMD9L, SBF1, SBF2, SCN11A, SCN1B, SCN2A, SCN2B, SCN3B, SCN4A, SCN4B, SCN5A, SCN9A, SCO2, SCYL1, SDHA, SELENOI, SELENON, SEPTIN1, SETX, SGCA, SGCB, SGCD, SGCE, SGCG, SGPL1, SH3TC2, SIGMAR1, SIL1, SIX1, SLC12A6, SLC16A1, SLC18A3, SLC1A3, SLC22A5, SLC25A1, SLC25A20, SLC25A26, SLC25A4, SLC25A42, SLC25A46, SLC33A1, SLC36A2, SLC52A2, SLC52A3, SLC5A7, SLC9A1, SLN, SMCHD1, SMN1, SMPD4, SMPX, SMTNL1, SMTNL2, SNAP25, SNTA1, SNUPN, SNX14, SOD1, SOD2, SORD, SOX8, SPART, SPAST, SPEG, SPG11, SPG21, SPG7, SPTAN1, SPTB, SPTBN2, SPTBN4, SPTLC1, SPTLC2, SPTSSA, SQSTM1, SRPK3, STAC3, STIM1, STUB1, SUCLA2, SUCLG1, SURF1, SVIL, SYNE1, SYNE2, SYPL2, SYT14, SYT2, TAFAZZIN, TARDBP, TBCK, TBK1, TBP, TCAP, TDP1, TDP2, TECPR2, TECRL, TEFM, TFG, TGFB3, TGM6, THAP11, THG1L, THOC2, TIA1, TIMM22, TK2, TMEM126B, TMEM168, TMEM233, TMEM240, TMEM38A, TMEM43, TMEM52, TMEM63C, TMEM65, TMOD4, TMPO, TNNC1, TNNC2, TNNI1, TNNI2, TNNI3, TNNT1, TNNT2, TNNT3, TNPO3, TOMM70, TOP3A, TOR1A, TOR1AIP1, TPM1, TPM2, TPM3, TPP1, TPT1, TRAPPC11, TRAPPC2L, TRDN, TRIM2, TRIM32, TRIM54, TRIM63, TRIM72, TRIP4, TRPC3, TRPV4, TSFM, TTBK2, TTN, TTPA, TTR, TUBA4A, TUBB3, TWNK, TXLNB, TXNIP, TYMP, UBA1, UBA5, UBAP1, UBC, UBQLN2, UCHL1, UCP3, UGDH, UNC13A, UNC45B, UNC50, VAMP1, VAPB, VCL, VCP, VEZF1, VGLL2, VHRT, VMA21, VPS13D, VPS37A, VPS41, VRK1, VWA1, VWA3B, WARS1, WASHC5, WDR73, WNK1, WWOX, XIRP2, XPNPEP3, XRCC1, YARS1, YARS2, YBX3, YIPF7, ZBTB42, ZC4H2, ZFHX2, ZFHX3, ZFYVE26, ZFYVE27

PATIENT REGISTRIES/ASSOCIATIONS

The genetic reports will also provide referring physicians of diagnosed patients with contact information for patient registries available preferably in the patient’s country of origin or other international registries. These registries are responsible for sharing information with patients and their families according to their own protocols.

Participation in registries is entirely voluntary and at the discretion of the patient and their family. Patient registries are important tools that systematically archive clinical and genetic data, with the primary aim of locating patients for clinical trials. Registries also serve as a support network for patients, offering additional resources that can assist throughout the course of the disease. The data contained in registries are valuable and contribute to advancing research and knowledge about neuromuscular diseases in the region.

Below, we provide a list of some registries and/or patient associations from various countries that we have compiled and will continue to update. However, this list is not exhaustive, so we recommend further investigation into other registries or associations in your country of residence

SMA (Spinal Muscular Atrophy): All LATAM ALAME: Alianza Latinoamericana AME O contactar a Claudia Sánchez | claudia.sanchez@amelatam.org | +44 7533 768502
Argentina Familias AME Argentina
Brasil INAME
Chile Corporación Familias AME Chile
Colombia Fundación AME Colombia Sara y Sofia “Famecol S&S” O contactar a Claudia Sánchez | registrodepacientes@famecolombia.org | +44 7533 768502
España CuidAME
México CurAME
Uruguay Familias con AME Uruguay
Reino Unido UK SMA Registry
República Dominicana CurAME
Lysosomal Storage Disorders and Glycogenoses. Pompe and Others: Colombia ACOPEL: Asociación Colombiana de Pacientes con Enfermedades de Depósito Lisosomal
GLUCOLATINO: Comunidad de Glucogenosis Hepática
Facioscapulohumeral Dystrophy (FSHD): Brasil ABRAFEUI & ABRAFEU II
Muscular Dystrophy, Duchenne, Becker, and Others: Argentina ADM: Asociación Distrofia Muscular
Brasil ADB
Chile DIMUS Chile: Asociación Distrofia Muscular Chile
Asociación ADN Chile
Colombia FCDM: Fundación Colombiana para Distrofia Muscular
Ecuador Registro Ecuatoriano de Distrofia de Duchenne
FEDIMURA: Federación ecuatoriana de Distrofia muscular
México Enlace (Chihuahua)
SMDM: Sociedad Mexicana de la Distrofia Muscular
Red Mexicana de Asociaciones de Distrofia Muscular
ALDIM: Asociación Leonesa para la Distrofia Muscular (León Guanajuato)
ADEMO: Asociación de Distrofia Muscular de Occidente (Guadalajara)
Juntos: Aves al vuelo
Asociación Duchenne Tijuana, A.C.
República Dominicana Thistrophy – Fundación Duchenne RD
Neuropathies: Brasil Charcot-Marie-Tooth: ABCMT
España Charcot-Marie-Tooth: EL MOTOR DE TUS PASOS
México Charcot-Marie-Tooth: FEMEXER
Reino Unido Charcot-Marie-Tooth: CMT UK
USA Charcot-Marie-Tooth: CMT Association
Various Charcot-Marie-Tooth: CMT Awareness
Various: Colombia FUNCOLEF: Fundación Colombiana para enfermedades Huérfanas
Fundación CdLS COLOMBIA
Reino Unido Registros Varios en Reino Unido

GENETIC COUNSELLING

The Latin-SEQ project is associated with a subproject called Latin-SEQ+, directed by Dr Lorraine Cowley, a genetic counsellor with extensive experience in counselling patients with rare diseases. Latin-SEQ+ focuses on exploring and improving the experiences of patients and healthcare providers in LATAM concerning the diagnosis of hereditary neuromuscular diseases through whole exome sequencing (WES) and whole genome sequencing (WGS).

This subproject aims to evaluate how genetic diagnoses impact medical care, prenatal testing opportunities, and the communication of genetic information within families. Additionally, it examines the cultural and religious impact on the acceptance of the diagnosis and subsequent measures taken. This study will not only contribute to the growth and improvement of genetic services in Latin America but also provide valuable insights for genetic counselling practice in the UK
.

Furthermore, Dr Lorraine Cowley will provide Latin-SEQ+ and Latin-SEQ participating physicians, clinicians, and other healthcare staff in LATAM with resources and training to better understand genetic results and effectively communicate them to patients and their families.

DIAGNOSTIC STRATEGY

The diagnostic strategy of Latin-SEQ uses an algorithm guided by the clinical suspicion of each patient as determined by the referring centre. Patients with hereditary neuromuscular diseases (NMDs) will be evaluated through specific genetic screening using Multiple Ligation Probe Amplification (MLPA) to rule out conditions such as Spinal Muscular Atrophy (SMA), Duchenne/Becker muscular dystrophy, and Charcot-Marie-Tooth neuropathies, or sequencing of recurrent mutations associated with congenital myasthenic syndromes and mitochondrial myopathies. This initial screening is expected to diagnose approximately 20% of cases. Cases not diagnosed through this method will proceed to whole exome sequencing.

In the first stage, exomes will be analysed focusing on a panel of over 600 genes related to neuromuscular diseases (based on http://www.musclegenetable.fr/) which will be updated every 6 months. This approach is expected to resolve 40-60% of cases. For unresolved cases, a more thorough analysis of the whole exome will be conducted, including sequencing of family members when possible. This approach will not only facilitate the diagnosis of rare diseases but also the identification of new genes. In such cases, studies will be conducted to validate the pathogenicity of identified variants and confirm their relevance using various criteria, including in silico analyses and functional studies in cellular or animal models.

In Latin-SEQ, the interpretation and analysis of genetic results follow a meticulous and rigorous process: the obtained data are analysed iteratively, and preliminary results are shared with referring physicians. These results are discussed in regular meetings to evaluate the findings based on the patient’s and family’s clinical presentation. For cases considered resolved, a final genetic report will be issued. For more complex cases, multidisciplinary meetings will be held where genetic results will be discussed alongside other available studies such as MRI or muscle biopsy.

GENETIC REPORTS

The genetic reports* issued by the coordinating team will provide information on the identified genetic variants and their classification according to the ACMG (American College of Medical Genetics and Genomics) guidelines, detailing each parameter included as well as relevant publications.

In genetic reports, the contact details of available PATIENT REGISTRIES/ASSOCIATIONS will be provided to the referring doctors, preferably within the country of origin or internationally, so they can share them with patients and their families in accordance with their protocols.

Unfortunately, the vast majority of NMDs have no cure or treatment; if any do, this information will also be included in the genetic reports. Clinical follow-up of patients is managed by the referring physicians.

*It is important to note that the results presented in these reports are obtained as part of a research study and therefore do not constitute a diagnostic credential. The interpretation and application of these data are the sole responsibility of the referring physicians. The Latin-SEQ team is not responsible for the use of the information contained in these reports.

*Please note that the analysis and interpretation provided in these reports depend on the correct identification of the samples and the accuracy of the clinical information provided.

Interpretation of Genetic Reports
POSITIVE:
LP/P variant(s) in a gene compatible with the phenotype
a) Heterozygous variant in an AD gene
b) Homozygous or compound heterozygous variants in an AR gene
COMPATIBLE:
a) Variant(s) of uncertain significance in a gene highly compatible with the phenotype
b) One heterozygous LP/P variant in an AR gene
INCONCLUSIVE:
Variant(s) of uncertain significance
(*) May change in the future
INCOMPATIBLE:
LP/P variant in a gene that is not compatible with the patient's phenotype
NEGATIVE:
No significant variants identified
(*) Study limitations
(**) May change in the future

LP/P: Likely Pathogenic/Pathogenic; AR: Autosomal Recessive; AD: Autosomal Dominant

Recurrent Variant Methodology

WES Methodology

  • 1

    Assay Method: Whole Exome Sequencing (WES), using the KAPA HyperExome capture kit (Roche) and the Illumina NovaSeq 6000 platform.

  • 2

    Bioinformatics Pipeline: Sequencing read mapping and identification of SNV/indel and CNV/SV variants are performed using DRAGEN v4.4.6. The resulting VCF files are annotated using VEP, SnpEff, SnpSift and InterVar for SNVs/indels, and AnnotSV for CNVs/SVs.

  • 3

    Data Analysis: The VCF files are uploaded to the Genome-Phenome Analysis Platform, GPAP, RD-Connect: https://platform.rd-connect.eu/#/

    Different filtering criteria are applied within the platform to identify potential disease-causing variants.

    During the primary analysis round, standard criteria commonly used for the genetic analysis of rare diseases are applied. These include a Minor Allele Frequency (MAF) of <1% in the control population, based on gnomAD v4.0, and a moderate or high Variant Effect Predictor (VEP) impact. This includes non-synonymous variants and in-frame indels, as well as truncating variants, such as nonsense variants, splice variants and frameshift indels.

    These criteria are assessed under different modes of inheritance, including recessive, dominant and X-linked inheritance. Single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy-number variants (CNVs) are analysed within the coding regions of the in silico panel applied.

    At this stage, the primary analysis panel is used, which contains 891 genes associated with NMDs. The complete list of genes is provided under PRIMARY GENE LIST.

    Where the initial analysis does not identify any relevant variants, a second round of analysis may be undertaken, guided by the patient’s phenotype.

    During this phase, expanded gene panels are applied according to the initial clinical suspicion and the discussions held during multidisciplinary meetings with the referring centre. This analysis may also include variants with a lower predicted impact, such as synonymous and intronic variants.

    Details of the secondary analysis performed for each patient are available upon request.

Segregation Methodology

  • 1

    Assay Method: PCR amplification and Sanger sequencing of variants of interest identified in the index case, using primers specific to each genomic region analysed.

  • 2

    Segregation Analysis: Variants are analysed in DNA samples from available relatives, both affected and unaffected, to determine their inheritance pattern and assess their co-segregation with the phenotype observed within the family.

    This analysis can also be used to establish the phase of compound heterozygous variants, determining whether they are located on different alleles, in trans, or on the same allele, in cis.

    The classification of a variant as de novo assumes that the stated biological relationships are correct, unless these relationships have been confirmed through other specific investigations.

The results are interpreted together with the family history, the expected mode of inheritance and the clinical information available.
Information on the primers used and the technical assay conditions is available upon request.

ACMG Classification

The genomic variants identified are classified in accordance with the original recommendations and pathogenicity criteria of the American College of Medical Genetics and Genomics, ACMG, Richards et al. 2015, as described under PATHOGENICITY EVIDENCE CRITERIA through freely available tools InterVar (https://wintervar.wglab.org/), Varsome (https://sso.varsome.com) and Franklin (https://franklin.genoox.com). Additional genetic and clinical information is manually curated.

The report also indicates whether the identified variant has previously been reported in the scientific literature or in clinical databases  (ClinVar and LOVD https://www.lovd.nl/). Please note that this information and the resulting classification may be subject to change, as described under LIMITATIONS.

Pathogenicity Evidence Criteria

  • Pathogenic Very Strong:

    • PVS1: Applied to protein-truncating variants, including nonsense, frameshift or splice variants, in genes where loss of function is an established disease mechanism.

  • Pathogenic Strong (PS):

    • PS1: The same amino acid change as a previously established pathogenic variant, but resulting from a different nucleotide change.
    • PS2: A confirmed de novo variant in the patient, with confirmation of both maternity and paternity.
    • PS3: Functional studies demonstrate a damaging effect consistent with the disease mechanism.
    • PS4: The variant is significantly more frequent in affected individuals than in unaffected individuals or controls.

  • Pathogenic Moderate (PM):

    • PM1: The variant is located within a functionally relevant region or mutational hot spot.
    • PM2: The variant is absent or present at a very low frequency in the control population, such as gnomAD.
    • PM3: In recessive disorders, the variant is detected in trans with another pathogenic variant.
    • PM4: The variant alters the length of the protein, such as an in-frame indel or stop-loss variant, in a gene where this is an established disease-causing mechanism.
    • PM5: A novel amino acid change affecting a residue where a different pathogenic alteration has previously been identified..
    • PM6: The variant is assumed to be de novo, without parental confirmation.

  • Pathogenic Supporting (PP):

    • PP1: Co-segregation with the disease in multiple affected relatives.
    • PP2: A missense variant in a gene with low tolerance to this type of variation and in which missense variants are an established cause of disease.
    • PP3: Multiple computational methods predict a deleterious effect, for example REVEL or CADD.
    • PP4: The patient’s clinical presentation and medical history are highly specific for the disease.
    • PP5: Previously reported by a reliable source. This criterion is considered obsolete by ClinGen and should be used with caution.

Limitations

The internal evaluation of the specificity and sensitivity of the variant-detection protocols using the Roche® KAPA HyperExome capture kit is 99.54% and 99.69%, respectively, for single-nucleotide variants, and 70.62% and 89.99%, respectively, for small insertions and deletions of up to 10 nucleotides.

Other types of genetic variants, such as repeat expansions, copy-number variants, structural variants or variants located in regions of high sequence homology, including pseudogenes and homologous regions, may not be detected.

This analysis also does not capture deep intronic variants, intergenic regions, or variants located within promoter or regulatory regions of a gene.

Consecutive variants forming haplotypes are not combined into multi-nucleotide variants (MNVs) and are reported as individual events.

Variants of uncertain significance (VUS) in genes that appear to be incompatible with the patient’s available clinical presentation are not included in the genetic reports, but may be provided upon request.

Variants identified during exome analysis are not systematically validated using an independent method. Where validation or an additional investigation is performed, this will be specified in the corresponding report.

Unless parental segregation studies are performed, the compound heterozygosity of variants and the biparental inheritance of homozygous variants are not confirmed and are only assumed.

In additional segregation studies performed using Sanger sequencing, the classification of a variant as de novo assumes that the stated biological relationships are correct, unless these relationships have been confirmed through other specific investigations.

Unless otherwise specified, each patient’s genomic data are analysed using an in silico panel of 891 genes associated with neuromuscular diseases. The complete list of genes included in this primary panel is provided under PRIMARY GENE LIST.

Genomic variants are classified according to the original recommendations of the American College of Medical Genetics and Genomics, ACMG, Richards et al. 2015.

Both the classification of variants and the interpretation of their diagnostic relevance are based on the scientific and clinical knowledge available at the time of analysis. They are therefore subject to change as new relevant information becomes available.

PRIMARY LIST OF GENES

This primary panel was created based on the most recent version of the Neuromuscular Gene Table (https://www.worldmusclesociety.org/page/gene-table) (Benarroch et al., 2025, https://pubmed.ncbi.nlm.nih.gov/41448968/). It has also been supplemented with information from public sources and unpublished internal data.

The list is reviewed approximately every six months.
Current version, July 2026, n=891:

AARS1, AARS2, ABCC9, ABCD3, ABHD16A, ABHD5, ABRA, ACAD9, ACADVL, ACTA1, ACTC1, ACTN2, ACTN3, ACVR1, ADAMTS15, ADCY6, ADGRG6, ADPRS, ADSS1, AFG3L2, AGL, AGRN, AHCY, AHNAK2, AIFM1, AKAP9, ALDH18A1, ALDH3A1, ALDH3A2, ALDOA, ALG14, ALG2, ALPK3, ALS2, AMFR, AMPD1, AMPD2, ANG, ANK2, ANKRD1, ANKRD2, ANKRD23, ANO10, ANO5, ANXA1, ANXA11, AP4B1, AP4E1, AP4M1, AP4S1, AP5Z1, APOBEC2, APOO, APTX, AR, ARHGAP19, ARHGEF10, ARL6IP1, ART1, ASAH1, ASB12, ASB2, ASB5, ASCC1, ASCC3, ATAD3A, ATG5, ATG7, ATL1, ATL3, ATM, ATP13A2, ATP1A1, ATP1A2, ATP1B4, ATP2A1, ATP2A2, ATP5F1B, ATP7A, ATXN1, ATXN10, ATXN2, ATXN3, ATXN7, ATXN8, ATXN8OS, B3GALNT2, B4GALNT1, B4GAT1, BAG3, BAG5, BEAN1, BEST3, BET1, BICD2, BIN1, BSCL2, C10orf71, C19orf12, C9orf72, CA3, CA8, CACNA1A, CACNA1C, CACNA1G, CACNA1H, CACNA1S, CACNB2, CACNB4, CACNG1, CACNG6, CADM3, CALM1, CALM2, CALM3, CALR3, CAP2, CAPN1, CAPN3, CAPNS1, CASQ1, CASQ2, CAV3, CAVIN1, CAVIN4, CCDC78, CCDC88C, CCT5, CDC40, CDH2, CELSR1, CFAP276, CFL2, CHAT, CHCHD10, CHD8, CHKB, CHMP2B, CHP1, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, CIAO1, CKM, CLCN1, CLN3, CLTCL1, CMYA5, CNBP, CNTN1, CNTNAP1, COA7, COL12A1, COL13A1, COL25A1, COL6A1, COL6A2, COL6A3, COLQ, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ9, COX15, COX16, COX18, COX20, COX6A1, COX6A2, CPT1C, CPT2, CRPPA, CRYAB, CSDE1, CSRP3, CTDP1, CTNNA3, CWF19L1, CYP2U1, CYP7B1, DAB1, DAG1, DARS2, DCAF8, DCTN1, DDHD1, DDHD2, DDIT4L, DES, DGAT2, DGUOK, DHTKD1, DMD, DMPK, DNA2, DNAJB2, DNAJB4, DNAJB6, DNM2, DNMT1, DOK7, DOLK, DPAGT1, DPM1, DPM2, DPM3, DSC2, DSG2, DSP, DST, DSTYK, DTNA, DUSP13B, DUSP29, DUX4, DYNC1H1, DYSF, ECEL1, EEF1A2, EEF2, EGF, EGR2, ELOVL4, ELOVL5, ELP1, EMD, EMILIN1, ENDOG, ENO3, ENTPD1, ENTPD5, ERBB3, ERBB4, ERLIN1, ERLIN2, ETFA, ETFB, ETFDH, EXOSC3, EXOSC8, EXOSC9, EYA4, FA2H, FABP3, FAM111B, FARS2, FASTKD2, FAT2, FBLN5, FBP2, FBXL4, FBXO32, FBXO38, FDX2, FEM1A, FGD4, FGF14, FHL1, FHL3, FHOD3, FICD, FIG4, FILIP1, FKRP, FKTN, FLAD1, FLII, FLNA, FLNC, FLVCR1, FOXK2, FTH1, FTL, FUS, FXN, FXR1, GAA, GAN, GAPDH, GARS1, GATAD1, GBA2, GBE1, GBF1, GDAP1, GDAP2, GFER, GFPT1, GGPS1, GIPC1, GJA5, GJB1, GJB3, GJC2, GLDN, GLE1, GLUL, GMPPB, GNB4, GNE, GOLGA2, GOSR2, GPD1L, GRID2, GRM1, GYG1, GYS1, H19, HACD1, HACE1, HARS1, HCN4, HEXB, HINT1, HJV, HK1, HMGCR, HMGCS1, HNRNPA1, HNRNPA2B1, HNRNPDL, HOXD10, HPDL, HRAS, HSP90AB1, HSPB1, HSPB3, HSPB6, HSPB7, HSPB8, HSPD1, HSPG2, IBA57, IDI2, IFRD1, IGFN1, IGHMBP2, ILK, INF2, INPP5K, IP6K3, ISCU, ITGA7, ITPR1, ITPR3, JAG1, JAG2, JPH1, JPH2, JSRP1, JUP, KARS1, KBTBD13, KCNA1, KCNA5, KCNA7, KCNC3, KCND3, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ11, KCNJ12, KCNJ18, KCNJ2, KCNJ5, KCNQ1, KIDINS220, KIF1A, KIF1B, KIF1C, KIF20A, KIF21A, KIF26B, KIF5A, KLC2, KLHL30, KLHL33, KLHL38, KLHL40, KLHL41, KLHL9, KPNA3, KY, L1CAM, LAMA2, LAMA4, LAMA5, LAMB2, LAMC1, LAMP2, LARGE1, LAS1L, LDB3, LDHA, LETM1, LIG3, LIMS2, LINGO4, LITAF, LMNA, LMOD2, LMOD3, LPCAT3, LPIN1, LRIF1, LRP10, LRP12, LRP4, LRRC38, LRSAM1, MACF1, MAFA, MAG, MAMDC2, MAP3K20, MAPT, MARS1, MARS2, MATR3, MB, MCM3AP, MCOLN1, MEGF10, MET, MFN2, MGME1, MIB1, MICU1, MIR1-1HG, MIR133A2, MKNK2, MLIP, MME, MORC2, MPDU1, MPV17, MPZ, MRE11, MRLN, MRPL3, MRPL44, MRPS25, MSTN, MSTO1, MT1X, MT2A, MT-CO1, MT-CO2, MT-CYB, MTHFSD, MTM1, MTMR2, MT-ND1, MTND1P23, MT-ND2, MTND2P28, MT-ND3, MT-ND4, MT-ND5, MT-ND6, MTO1, MTPAP, MTRFR, MT-RNR1, MT-RNR2, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY, MUSK, MYADML2, MYBPC1, MYBPC2, MYBPC3, MYBPH, MYF6, MYH1, MYH14, MYH2, MYH3, MYH6, MYH7, MYH8, MYL1, MYL11, MYL12A, MYL2, MYL3, MYL4, MYLK2, MYMK, MYMX, MYO18B, MYO9A, MYO9B, MYOD1, MYOG, MYOM3, MYOT, MYOZ1, MYOZ2, MYOZ3, MYPN, NAA10, NAGLU, NARS1, NBAS, NDRG1, NDUFAF1, NDUFB10, NEB, NEFH, NEFL, NEK1, NEK9, NEXN, NFU1, NGF, NHERF1, NIPA1, NKX6-2, NMNAT2, NOP56, NOTCH2NLC, NPPA, NPTX1, NRAP, NSUN3, NT5C2, NTRK1, NUP155, NUP88, NUTM2B-AS1, OBSCN, OGDHL, OPA1, OPTN, ORAI1, OXA1L, PABPN1, PACSIN3, PAX7, PCNA, PCYT2, PDK3, PDK4, PDLIM3, PDYN, PERM1, PEX7, PFKM, PFN1, PGAM2, PGK1, PGM1, PGPEP1L, PHKA1, PHKG1, PHOX2A, PHYH, PI4KA, PIEZO2, PIGK, PIP5K1C, PITRM1, PITX2, PKP2, PLD3, PLEC, PLEKHG5, PLIN4, PLN, PLP1, PMP2, PMP22, PMPCA, PNKP, PNPLA2, PNPLA6, PNPLA8, PNPT1, POC1A, POC1B, POC5, POGLUT1, POLG, POLG2, POLR3B, POMGNT1, POMGNT2, POMK, POMT1, POMT2, POPDC1, POPDC3, PPCS, PPDPFL, PPP1R27, PPP2R2B, PRDM12, PRDM16, PRDX3, PRECSIT, PREPL, PRKAG2, PRKAG3, PRKCG, PRPH, PRPS1, PRUNE1, PRX, PSAT1, PSEN1, PSEN2, PSMB4, PTPN11, PTRH2, PUM1, PURA, PUS1, PYGM, PYROXD1, RAB7A, RAF1, RAPSN, RBCK1, RBFOX1, RBM20, RBM7, REEP1, REEP2, RETREG1, RFC1, RFC4, RILPL1, RNASEH1, RNASEH1P1, RNF170, RNF216, RNF220, RNU4-2, RPH3A, RPL10, RPL18AP3, RPL19, RPL26, RPL27, RPL3L, RPLP0, RPLP1, RPLP2, RPS11, RPS12, RPS13, RPS16, RPS18, RRM2B, RTN2, RUBCN, RXYLT1, RYR1, RYR2, RYR3, SACS, SAMD9L, SBF1, SBF2, SCN11A, SCN1B, SCN2A, SCN2B, SCN3B, SCN4A, SCN4B, SCN5A, SCN9A, SCO2, SCYL1, SDHA, SELENOI, SELENON, SEPTIN1, SETX, SGCA, SGCB, SGCD, SGCE, SGCG, SGPL1, SH3TC2, SIGMAR1, SIL1, SIX1, SLC12A6, SLC16A1, SLC18A3, SLC1A3, SLC22A5, SLC25A1, SLC25A20, SLC25A26, SLC25A4, SLC25A42, SLC25A46, SLC33A1, SLC36A2, SLC52A2, SLC52A3, SLC5A7, SLC9A1, SLN, SMCHD1, SMN1, SMPD4, SMPX, SMTNL1, SMTNL2, SNAP25, SNTA1, SNUPN, SNX14, SOD1, SOD2, SORD, SOX8, SPART, SPAST, SPEG, SPG11, SPG21, SPG7, SPTAN1, SPTB, SPTBN2, SPTBN4, SPTLC1, SPTLC2, SPTSSA, SQSTM1, SRPK3, STAC3, STIM1, STUB1, SUCLA2, SUCLG1, SURF1, SVIL, SYNE1, SYNE2, SYPL2, SYT14, SYT2, TAFAZZIN, TARDBP, TBCK, TBK1, TBP, TCAP, TDP1, TDP2, TECPR2, TECRL, TEFM, TFG, TGFB3, TGM6, THAP11, THG1L, THOC2, TIA1, TIMM22, TK2, TMEM126B, TMEM168, TMEM233, TMEM240, TMEM38A, TMEM43, TMEM52, TMEM63C, TMEM65, TMOD4, TMPO, TNNC1, TNNC2, TNNI1, TNNI2, TNNI3, TNNT1, TNNT2, TNNT3, TNPO3, TOMM70, TOP3A, TOR1A, TOR1AIP1, TPM1, TPM2, TPM3, TPP1, TPT1, TRAPPC11, TRAPPC2L, TRDN, TRIM2, TRIM32, TRIM54, TRIM63, TRIM72, TRIP4, TRPC3, TRPV4, TSFM, TTBK2, TTN, TTPA, TTR, TUBA4A, TUBB3, TWNK, TXLNB, TXNIP, TYMP, UBA1, UBA5, UBAP1, UBC, UBQLN2, UCHL1, UCP3, UGDH, UNC13A, UNC45B, UNC50, VAMP1, VAPB, VCL, VCP, VEZF1, VGLL2, VHRT, VMA21, VPS13D, VPS37A, VPS41, VRK1, VWA1, VWA3B, WARS1, WASHC5, WDR73, WNK1, WWOX, XIRP2, XPNPEP3, XRCC1, YARS1, YARS2, YBX3, YIPF7, ZBTB42, ZC4H2, ZFHX2, ZFHX3, ZFYVE26, ZFYVE27

PATIENT REGISTRIES/ASSOCIATIONS

The genetic reports will also provide referring physicians of diagnosed patients with contact information for patient registries available preferably in the patient’s country of origin or other international registries. These registries are responsible for sharing information with patients and their families according to their own protocols.

Participation in registries is entirely voluntary and at the discretion of the patient and their family. Patient registries are important tools that systematically archive clinical and genetic data, with the primary aim of locating patients for clinical trials. Registries also serve as a support network for patients, offering additional resources that can assist throughout the course of the disease. The data contained in registries are valuable and contribute to advancing research and knowledge about neuromuscular diseases in the region.

Below, we provide a list of some registries and/or patient associations from various countries that we have compiled and will continue to update. However, this list is not exhaustive, so we recommend further investigation into other registries or associations in your country of residence

SMA (Spinal Muscular Atrophy): All LATAM ALAME: Alianza Latinoamericana AME O contactar a Claudia Sánchez | claudia.sanchez@amelatam.org | +44 7533 768502
Argentina Familias AME Argentina
Brasil INAME
Chile Corporación Familias AME Chile
Colombia Fundación AME Colombia Sara y Sofia “Famecol S&S” O contactar a Claudia Sánchez | registrodepacientes@famecolombia.org | +44 7533 768502
España CuidAME
México CurAME
Uruguay Familias con AME Uruguay
Reino Unido UK SMA Registry
República Dominicana CurAME
Lysosomal Storage Disorders and Glycogenoses. Pompe and Others: Colombia ACOPEL: Asociación Colombiana de Pacientes con Enfermedades de Depósito Lisosomal
GLUCOLATINO: Comunidad de Glucogenosis Hepática
Facioscapulohumeral Dystrophy (FSHD): Brasil ABRAFEUI & ABRAFEU II
Muscular Dystrophy, Duchenne, Becker, and Others: Argentina ADM: Asociación Distrofia Muscular
Brasil ADB
Chile DIMUS Chile: Asociación Distrofia Muscular Chile
Asociación ADN Chile
Colombia FCDM: Fundación Colombiana para Distrofia Muscular
Ecuador Registro Ecuatoriano de Distrofia de Duchenne
FEDIMURA: Federación ecuatoriana de Distrofia muscular
México Enlace (Chihuahua)
SMDM: Sociedad Mexicana de la Distrofia Muscular
Red Mexicana de Asociaciones de Distrofia Muscular
ALDIM: Asociación Leonesa para la Distrofia Muscular (León Guanajuato)
ADEMO: Asociación de Distrofia Muscular de Occidente (Guadalajara)
Juntos: Aves al vuelo
Asociación Duchenne Tijuana, A.C.
República Dominicana Thistrophy – Fundación Duchenne RD
Neuropathies: Brasil Charcot-Marie-Tooth: ABCMT
España Charcot-Marie-Tooth: EL MOTOR DE TUS PASOS
México Charcot-Marie-Tooth: FEMEXER
Reino Unido Charcot-Marie-Tooth: CMT UK
USA Charcot-Marie-Tooth: CMT Association
Various Charcot-Marie-Tooth: CMT Awareness
Various: Colombia FUNCOLEF: Fundación Colombiana para enfermedades Huérfanas
Fundación CdLS COLOMBIA
Reino Unido Registros Varios en Reino Unido

GENETIC COUNSELLING

The Latin-SEQ project is associated with a subproject called Latin-SEQ+, directed by Dr Lorraine Cowley, a genetic counsellor with extensive experience in counselling patients with rare diseases. Latin-SEQ+ focuses on exploring and improving the experiences of patients and healthcare providers in LATAM concerning the diagnosis of hereditary neuromuscular diseases through whole exome sequencing (WES) and whole genome sequencing (WGS).

This subproject aims to evaluate how genetic diagnoses impact medical care, prenatal testing opportunities, and the communication of genetic information within families. Additionally, it examines the cultural and religious impact on the acceptance of the diagnosis and subsequent measures taken. This study will not only contribute to the growth and improvement of genetic services in Latin America but also provide valuable insights for genetic counselling practice in the UK
.

Furthermore, Dr Lorraine Cowley will provide Latin-SEQ+ and Latin-SEQ participating physicians, clinicians, and other healthcare staff in LATAM with resources and training to better understand genetic results and effectively communicate them to patients and their families.