Protein and genetic diagnosis of limb girdle muscular dystrophy type 2A: The yield and the pitfalls

2015 ◽  
Vol 52 (2) ◽  
pp. 163-173 ◽  
Author(s):  
Marina Fanin ◽  
Corrado Angelini
Keyword(s):  
Muscular Dystrophy ◽  
Genetic Diagnosis ◽  
Limb Girdle Muscular Dystrophy

Elucidation of the Genetic Cause in Dutch Limb Girdle Muscular Dystrophy Families: A 27-Year’s Journey

2020 ◽  
pp. 1-12
Author(s):  
L. Ten Dam ◽  
M. de Visser ◽  
H.B. Ginjaar ◽  
H.A. van Duyvenvoorde ◽  
S. van Koningsbruggen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Muscular Dystrophy ◽  
Dna Analysis ◽  
Genetic Diagnosis ◽  
Limb Girdle Muscular Dystrophy ◽  
Facioscapulohumeral Dystrophy ◽  
Related Family ◽  
Whole Exome ◽  
Made In

Background: A Dutch cohort of 105 carefully selected limb girdle muscular dystrophy 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 (LGMD) 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 α-, β- and γ-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.

Mutational Spectrum of CAPN3 with Genotype-Phenotype Correlations in Limb Girdle Muscular Dystrophy Type 2A/R1 (LGMD2A/LGMDR1) Patients in India

2021 ◽  
Vol 8 (1) ◽  
pp. 125-136
Author(s):  
Pankaj Pathak ◽  
Mehar Chand Sharma ◽  
Pankaj Jha ◽  
Chitra Sarkar ◽  
Mohammed Faruq ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Genetic Diagnosis ◽  
European Population ◽  
Significant Loss ◽  
Limb Girdle Muscular Dystrophy ◽  
Calpain 3 ◽  
Recessive Type ◽  
Slow Progression ◽  
Significant Burden ◽  
Progression Of Disease

Background: Limb girdle muscular dystrophy recessive type 1 (LGMDR1, Previously LGMD2A) is characterized by inactivating mutations in CAPN3. Despite the significant burden of muscular dystrophy in India, and particularly of LGMDR1, its genetic characterization and possible phenotypic manifestations are yet unidentified. Material and Methods: We performed bidirectional CAPN3 sequencing in 95 LGMDR1 patient samples characterized by calpain-3 protein analysis, and these findings were correlated with clinical, biochemical and histopathological features. Results: We identified 84 (88.4%) cases of LGMDR1 harboring 103 CAPN3 mutations (71 novel and 32 known). At least two mutant alleles were identified in 79 (94.2%) of patients. Notably, 76% exonic variations were enriched in nine CAPN3 exons and overall, 41 variations (40%) correspond to only eight exonic and intronic mutations. Patients with two nonsense/out of frame/splice-site mutations showed significant loss of calpain-3 protein as compared to those with two missense/inframe mutations (P = 0.04). We observed a slow progression of disease and less severity in our patients compared to European population. Rarely, presenting clinical features were atypical, and mimicked other muscle diseases like FSHMD, distal myopathy and metabolic myopathies. Conclusion: This is first systematic study to characterize the genetic framework of LGMDR1 in the Indian population. Preliminary calpain-3 immunoblot screening serves well to direct genetic testing. Our findings prioritized nine CAPN3 exons for LGMDR1 diagnosis in our population; therefore, a targeted-sequencing panel of nine exons could serve well for genetic diagnosis, carrier testing, counseling and clinical trial feasibility study in LGMDR1 patients in India.

scholarly journals A slowly progressive form of limb‐girdle muscular dystrophy type 2C associated with founder mutation in the SGCG gene in Puerto Rican Hispanics

2015 ◽  
Vol 3 (2) ◽  
pp. 92-98 ◽  
Author(s):  
Samiah A. Al‐Zaidy ◽  
Vinod Malik ◽  
Kelley Kneile ◽  
Xiomara Q. Rosales ◽  
Ana Maria Gomez ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Puerto Rican ◽  
Founder Mutation ◽  
Limb Girdle Muscular Dystrophy ◽  
Progressive Form
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