| Title: |
A case of pseudodominant inheritance of limb-girdle muscular dystrophy caused by mutations in the CAPN3 gene |
| Authors: |
Inna V. Sharkova; Maria V. Bulakh; Liudmila А. Bessonova; Olga A. Shchagina; Elena L. Dadaly |
| Source: |
Анналы клинической и экспериментальной неврологии, Vol 15, Iss 3, Pp 85-91 (2021) |
| Publisher Information: |
Research Center of Neurology |
| Publication Year: |
2021 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
limb-girdle muscular dystrophy; autosomal recessive lgmd; calpainopathy; calpain-3-related muscular dystrophy; capn3 gene; pseudodominant inheritance; case report; Neurosciences. Biological psychiatry. Neuropsychiatry; RC321-571 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English; Russian |
| Relation: |
https://annaly-nevrologii.com/journal/pathID/article/viewFile/762/592; https://doaj.org/toc/2075-5473; https://doaj.org/toc/2409-2533; https://doaj.org/article/eac3f5daff8643a3b8e7de4daae883e1 |
| DOI: |
10.54101/ACEN.2021.3.10 |
| Availability: |
https://doi.org/10.54101/ACEN.2021.3.10; https://doaj.org/article/eac3f5daff8643a3b8e7de4daae883e1 |
| Accession Number: |
edsbas.1531946E |
| Database: |
BASE |