Novel splicing dysferlin mutation causing myopathy with intra-familial heterogeneity
| Autor: | Leila Lehkim, François-Jérôme Authier, Sawsan Ben Romdhane, Nouha Farhat, Salma Sakka, Mariem Dammak, Khaireddine Ben Mahfoudh, Yasmine Baba Amer, Sabrine Rekik, Chokri Mhiri |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Dysferlinopathy RNA Splicing Biology Dysferlin 03 medical and health sciences Exon 0302 clinical medicine Muscular Diseases Genetics medicine Humans Genetic Predisposition to Disease Myopathy Molecular Biology Gene Muscle biopsy medicine.diagnostic_test High-Throughput Nucleotide Sequencing General Medicine Middle Aged medicine.disease 030104 developmental biology Phenotype Muscular Dystrophies Limb-Girdle 030220 oncology & carcinogenesis Mutation (genetic algorithm) RNA splicing Mutation biology.protein Female medicine.symptom |
| Zdroj: | Molecular biology reports. 47(8) |
| ISSN: | 1573-4978 |
| Popis: | Dysferlinopathies belong to the heterogeneous group of autosomal recessive muscular disorders, caused by mutations in the dysferlin gene and characterized by a high degree of clinical variability even though within the same family. This study aims to describe three cases, belonging to a consanguineous Tunisian family, sharing a new splicing mutation in the dysferlin gene and presenting intra-familial variability of dysferlinopathies: Proximal–distal weakness and distal myopathy with anterior tibial onset. We performed the next generation sequencing for mutation screening and reverse transcriptase-PCR for gene expression analysis. Routine muscle histology was used for muscle biopsy processing. The clinical presentation demonstrated heterogeneous phenotypes between the three cases: Two presented intermediate phenotypes of dysferlinopathy with proximal–distal weakness and the third had a distal myopathy with anterior tibial onset. Genetic analysis yielded a homozygous splicing mutation (c.4597-2A>G) in the dysferlin gene, giving rise to the suppression of 28 bp of the exon 43. The splicing mutation found in our family (c.4597-2A>G) is responsible for the suppression of 28 bp of the exon 43 and a wide clinical intra-familial variability. |
| Databáze: | OpenAIRE |
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