TY - JOUR
T1 - Elucidation of the Genetic Cause in Dutch Limb Girdle Muscular Dystrophy Families: A 27-Year's Journey
AU - ten Dam, L.
AU - de Visser, M.
AU - Ginjaar, Ieke B.
AU - van Duyvenvoorde, Hermine A.
AU - van Koningsbruggen, Silvana
AU - van der Kooi, Anneke J.
N1 - Funding Information: The data that support the findings of this study are available from the corresponding author upon reasonable request. Publisher Copyright: © 2021 - IOS Press. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - Background: A Dutch cohort of 105 carefully selected limb girdle muscular dystrophy (LGMD) patients from 68 families has been subject to genetic testing over the last 20 years. After subsequent targeted gene analysis around two thirds (45/68) of the families had received a genetic diagnosis in 2013. Objective: To describe the results of further genetic testing in the remaining undiagnosed limb girdle muscular dystrophy families in this cohort. Methods: In the families of the cohort for whom no genetic diagnosis was established (n = 23) further testing using Sanger sequencing, next generation sequencing with gene panel analysis or whole-exome sequencing was performed. In one case DNA analysis for facioscapulohumeral dystrophy type 1 was carried out. Results: In eight families no additional genetic tests could be performed. In 12 of the remaining 15 families in which additional testing could be performed a genetic diagnosis was established: two LGMDR1 calpain3-related families with CAPN3 mutations, one LGMDR2 dysferlin-related family with DYSF mutations, three sarcoglycanopathy families (LGMDR3-5 a-, ß- and ?-sarcoglycan-related) with SGCA/SGCB/SGCG mutations, one LGMDR8 TRIM 32-related family with TRIM32 mutations, two LGMDR19 GMPPB-related families with GMPPB mutations, one family with MICU1-related myopathy, one family with FLNC-related myopathy and one family with facioscapulohumeral dystrophy type 1. At this moment a genetic diagnosis has been made in 57 of the 60 families of which DNA was available (95%). Conclusion: A genetic diagnosis is obtained in 95% of the families of the original Dutch LGMD cohort of which DNA was available.
AB - Background: A Dutch cohort of 105 carefully selected limb girdle muscular dystrophy (LGMD) patients from 68 families has been subject to genetic testing over the last 20 years. After subsequent targeted gene analysis around two thirds (45/68) of the families had received a genetic diagnosis in 2013. Objective: To describe the results of further genetic testing in the remaining undiagnosed limb girdle muscular dystrophy families in this cohort. Methods: In the families of the cohort for whom no genetic diagnosis was established (n = 23) further testing using Sanger sequencing, next generation sequencing with gene panel analysis or whole-exome sequencing was performed. In one case DNA analysis for facioscapulohumeral dystrophy type 1 was carried out. Results: In eight families no additional genetic tests could be performed. In 12 of the remaining 15 families in which additional testing could be performed a genetic diagnosis was established: two LGMDR1 calpain3-related families with CAPN3 mutations, one LGMDR2 dysferlin-related family with DYSF mutations, three sarcoglycanopathy families (LGMDR3-5 a-, ß- and ?-sarcoglycan-related) with SGCA/SGCB/SGCG mutations, one LGMDR8 TRIM 32-related family with TRIM32 mutations, two LGMDR19 GMPPB-related families with GMPPB mutations, one family with MICU1-related myopathy, one family with FLNC-related myopathy and one family with facioscapulohumeral dystrophy type 1. At this moment a genetic diagnosis has been made in 57 of the 60 families of which DNA was available (95%). Conclusion: A genetic diagnosis is obtained in 95% of the families of the original Dutch LGMD cohort of which DNA was available.
KW - Limb girdle muscular dystrophy
KW - gene panel
KW - sanger sequencing
KW - whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85102116706&partnerID=8YFLogxK
U2 - https://doi.org/10.3233/JND-200585
DO - https://doi.org/10.3233/JND-200585
M3 - Article
C2 - 33386810
SN - 2214-3599
VL - 8
SP - 261
EP - 272
JO - Journal of neuromuscular diseases
JF - Journal of neuromuscular diseases
IS - 2
ER -