Dataset Information

Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy.

ABSTRACT: BACKGROUND:Dysferlinopathy is caused by mutations in the dysferlin (DYSF) gene. Here, we described the genetic features of a large cohort of Chinese patients with this disease. METHODS:Eighty-nine index patients were included in the study. DYSF gene analysis was performed by Sanger sequencing in 41 patients and targeted next generation sequencing (NGS) in 48 patients. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect exon duplication/deletion in patients with only one pathogenic mutation. RESULTS:Among the 89 index patients, 79 patients were demonstrated to carry two disease-causing (73 cases) or possibly disease-causing mutations (6 cases), including 26 patients with homozygous mutations. We identified 105 different mutations, including 59 novel ones. Notably, in 13 patients in whom only one pathogenic mutation was initially found by Sanger sequencing or NGS, 3 were further identified to carry exon deletions by MLPA. The mutations identified in this study appeared to cluster in the N-terminal region. Mutation types included missense mutations (30.06%), nonsense mutations (17.18%), frameshift mutations (30.67%), in-frame deletions (2.45%), intronic mutations (17.79%), and exonic rearrangement (1.84%). No genotype-phenotype correlation was identified. CONCLUSIONS:DYSF mutations in Chinese patients clustered in the N-terminal region of the gene. Exonic rearrangements were found in 23% of patients with only one pathogenic mutation identified by Sanger sequencing or NGS. The novel mutations found in this study greatly expanded the mutational spectrum of dysferlinopathy.

SUBMITTER: Jin SQ

PROVIDER: S-EPMC5040013 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy.

Jin Su-Qin SQ Yu Meng M Zhang Wei W Lyu He H Yuan Yun Y Wang Zhao-Xia ZX

Chinese medical journal 20161001 19

<h4>Background</h4>Dysferlinopathy is caused by mutations in the dysferlin (DYSF) gene. Here, we described the genetic features of a large cohort of Chinese patients with this disease.<h4>Methods</h4>Eighty-nine index patients were included in the study. DYSF gene analysis was performed by Sanger sequencing in 41 patients and targeted next generation sequencing (NGS) in 48 patients. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect exon duplication/deletion in patie ...[more]

PMID: 27647186

Similar Datasets

Project description:BACKGROUND:Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D, LGMD2E, and LGMD2F) that are caused, respectively, by mutations in the SGCG, SGCA, SGCB, and SGCD genes. Knowledge about the clinical and genetic features of sarcoglycanopathies in Chinese patients is limited. The aims of this study were to investigate in detail the clinical manifestations, sarcoglycan expression, and gene mutations in Chinese patients with sarcoglycanopathies and to identify possible correlations between them. RESULTS:Of 3638 patients for suspected neuromuscular diseases (1733 with inherited myopathies, 1557 with acquired myopathies, and 348 unknown), 756 patients had next-generation sequencing (NGS) diagnostic panel. Twenty-five patients with sarcoglycanopathies (11.5%) were identified from 218 confirmed LGMDs, comprising 18 with LGMD2D, 6 with LGMD2E, and one with LGMD2C. One patient with LGMD2D also had Charcot-Marie-Tooth 1A. The clinical phenotypes of the patients with LGMD2D or LGMD2E were markedly heterogeneous. Muscle biopsy showed a dystrophic pattern in 19 patients and mild myopathic changes in 6. The percentage of correct prediction of genotype based on expression of sarcoglycan was 36.0% (4 LGMD2D, 4 LGMD2E, and one LGMD2C). There was a statistically significant positive correlation between reduction of ?-sarcoglycan level and disease severity in LGMD2D. Thirty-five mutations were identified in SGCA, SGCB, SGCG, and PMP22, 16 of which were novel. Exon 3 of SGCA was a hotspot region for mutations in LGMD2D. The missense mutation c.662G?>?A (p.R221H) was the most common mutation in SGCA. Missense mutations in both alleles of SGCA were associated with a relative benign disease course. No obvious clinical, sarcoglycan expression, and genetic correlation was found in LGMD2E. CONCLUSIONS:This study expands the clinical and genetic spectrum of sarcoglycanopathies in Chinese patients and provides evidence that disease severity of LGMD2D may be predicted by ?-sarcoglycan expression and SGCA mutation.

Dataset Information

Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy.

Publications

Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets