Dataset Information

Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q.

ABSTRACT: Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogenous group of disorders, with both recessive and dominant forms reported. Recently, a series of recessive LGMD families were linked to chromosome 15q. We report herein the results of our linkage studies in a previously reported large autosomal dominant family. The LGMD gene in this family was localized to chromosome 5q22.3-31.3 by using a series of CA(n) microsatellite repeat markers. Linkage to 15q was excluded. These findings confirm genetic heterogeneity in this clinically diverse syndrome.

SUBMITTER: Speer MC

PROVIDER: S-EPMC1682558 | biostudies-other | 1992 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q.

Speer M C MC Yamaoka L H LH Gilchrist J H JH Gaskell C P CP Stajich J M JM Vance J M JM Kazantsev A A Lastra A A AA Haynes C S CS Beckmann J S JS

American journal of human genetics 19920601 6

Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogenous group of disorders, with both recessive and dominant forms reported. Recently, a series of recessive LGMD families were linked to chromosome 15q. We report herein the results of our linkage studies in a previously reported large autosomal dominant family. The LGMD gene in this family was localized to chromosome 5q22.3-31.3 by using a series of CA(n) microsatellite repeat markers. Linkage to 15q was excluded. These ...[more]

PMID: 1598902

Similar Datasets

Project description:ObjectiveTo identify novel biomarkers as an alternative diagnostic tool for limb girdle muscular dystrophy (LGMD).BackgroundLGMD encompasses a group of muscular dystrophies characterized by proximal muscles weakness, elevated CK levels and dystrophic findings on muscle biopsy. Heterozygous CAPN3 mutations are associated with autosomal dominant LGMD-4, while biallelic mutations can cause autosomal recessive LGMD-1. Diagnosis is currently often based on invasive methods requiring muscle biopsy or blood tests. In most cases Western blotting (WB) analysis from muscle biopsy is essential for a diagnosis, as muscle samples are currently the only known tissues to express the full-length CAPN3 isoform.MethodsWe analyzed CAPN3 in a cohort including 60 LGMD patients. Selected patients underwent a complete neurological examination, electromyography, muscle biopsy, and skin biopsies for primary fibroblasts isolation. The amount of CAPN3 was evaluated by WB analysis in muscle and skin tissues. The total RNA isolated from muscle, fibroblast and urine was processed, and cDNA was used for qualitative analysis. The expression of CAPN3 was investigated by qRT-PCR. The CAPN3 3D structure has been visualized and analyzed using PyMOL.ResultsAmong our patients, seven different CAPN3 mutations were detected, of which two were novel. After sequencing CAPN3 transcripts from fibroblast and urine, we detected different CAPN3 isoforms surprisingly including the full-length transcript. We found comparable protein levels from fibroblasts and muscle tissue; in particular, patients harboring a novel CAPN3 mutation showed a 30% reduction in protein compared to controls from both tissues.ConclusionsOur findings showed for the first time the presence of the CAPN3 full-length transcript in urine and skin samples. Moreover, we demonstrated surprisingly comparable CAPN3 protein levels between muscle and skin samples, thus allowing us to hypothesize the use of skin biopsy and probably of urine samples as an alternative less invasive method to assess the amount of CAPN3 when molecular diagnosis turns out to be inconclusive.

Dataset Information

Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q.

Publications

Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets