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- Title
A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H.
- Authors
Bisceglia, Luigi; Zoccolella, Stefano; Torraco, Alessandra; Piemontese, Maria Rosaria; Dell'Aglio, Rosa; Amati, Angela; De Bonis, Patrizia; Artuso, Lucia; Copetti, Massimiliano; Santorelli, Filippo Maria; Serlenga, Luigi; Zelante, Leopoldo; Bertini, Enrico; Petruzzella, Vittoria
- Abstract
Limb-girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of neuromuscular disorders with a selective or predominant involvement of shoulder and pelvic girdles. We clinically examined 19 members in a four-generation Italian family with autosomal-dominant LGMD. A total of 11 subjects were affected. Clinical findings showed variable expressivity in terms of age at onset and disease severity. Five subjects presented with a slowly progressive proximal muscle weakness, in both upper and lower limbs, with onset during the fourth-fifth decade of life, which fulfilled the consensus diagnostic criteria for LGMD. Earlier onset of the disease was observed in a group of patients presenting with muscle weakness and/or calf hypertrophy, and/or occasionally high CK and lactate serum levels. Two muscle biopsies showed morphological findings compatible with MD associated with subsarcolemmal accumulation of mitochondria and the presence of multiple mitochondrial DNA deletions. A genome-wide scan performed using microsatellite markers mapped the disease on chromosome 3p23-p25.1 locus in a 25-cM region between markers D3S1263 and D3S3685. The highest two-point LOD score was 3.26 (theta=0) at marker D3S1286 and D3S3613, whereas non-parametric analysis reached a P-value=0.0004. Four candidate genes within the refined region were analysed but did not reveal any mutations. Our findings further expand the clinical and genetic heterogeneity of LGMDs.
- Publication
European journal of human genetics : EJHG, 2010, Vol 18, Issue 6, p636
- ISSN
1476-5438
- Publication type
Journal Article
- DOI
10.1038/ejhg.2009.235