A case of pseudodominant inheritance of limb-girdle muscular dystrophy caused by mutations in the CAPN3 gene
Autor: | Inna V. Sharkova, Maria V. Bulakh, Liudmila А. Bessonova, Olga A. Shchagina, Elena L. Dadaly |
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Jazyk: | English<br />Russian |
Rok vydání: | 2021 |
Předmět: | |
Zdroj: | Анналы клинической и экспериментальной неврологии, Vol 15, Iss 3, Pp 85-91 (2021) |
Druh dokumentu: | article |
ISSN: | 2075-5473 2409-2533 |
DOI: | 10.54101/ACEN.2021.3.10 |
Popis: | Introduction. Limb-girdle muscular dystrophy (LGMD) includes more than 30 forms caused by mutations in genes located on autosomes. The most common form is calpain-3-related LGMD, with autosomal recessive inheritance pattern (OMIM 253600). An autosomal dominant form of LGMD (OMIM 618129) caused by c.643_663del heterozygous mutation in the CAPN3 gene is also supposed to exist. This article describes a family case of LGMD caused by mutations in the CAPN3 gene with pseudodominant inheritance. Materials and methods. Two patients with LGMD were studied: a 59-year-old woman and her 38-year-old daughter. Clinical, genealogical and molecular genetics methods were used: limb girdle muscular dystrophy MPS panel, Sanger sequencing of DNA of the proband, her affected daughter, and six first- and second-degree relatives across four generations. Results. It was found that identical variants of the nucleotide sequence, c.598_612del and c.1746-20CG, identified in the CAPN3 gene of the proband and her daughter, are in the trans position (compound heterozygous state), causing autosomal recessive calpain-3-related LGMD. This is an example of an incredibly rare pseudodominant inheritance of an autosomal recessive disease, established through indirect evidence that the probands husband is a heterozygous carrier of a nucleotide substitution in the CAPN3 gene. Conclusion. It is crucial to examine the marriage partner for heterozygous carrier status of a gene mutation responsible for the disease in family planning and when clarifying the childs prognosis for a patient with an autosomal recessive disease. Considering the existence of a late-onset (after 30 years) LGMD phenotype associated with the CAPN3 gene, differential diagnosis should begin with testing this gene in families with late disease onset. |
Databáze: | Directory of Open Access Journals |
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