A new locus on 3p23–p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H

• Published in: European journal of human genetics : EJHG Vol. 18; no. 6; pp. 636 - 641
• Main 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
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2010; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/337/103; 692/699/375/374; Adolescent; Adult; Age; Aged; Biochemistry; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Child; Chromosome 3; Chromosome Disorders - genetics; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 3 - genetics; Classical genetics, quantitative genetics, hybrids; Cytogenetics; Deoxyribonucleic acid; Disease; DNA; Dystrophy; Family; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; General aspects. Genetic counseling; Genes; Genes, Dominant - genetics; Genetic markers; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Haplotypes; Human; Human Genetics; Humans; Hypertrophy; Kinases; Lactic acid; Limbs; Male; Medical genetics; Medical sciences; Microsatellites; Middle Aged; Mitochondrial DNA; Molecular and cellular biology; Morphology; Muscular Dystrophies, Limb-Girdle - genetics; Muscular dystrophy; Mutation; Neurology; Neuromuscular system; Pedigree; Serum levels; Shoulder; Young Adult; Italy; autosomal-dominant limb-girdle muscular dystrophy; linkage analysis; multiple mtDNA deletions; chromosome 3; Chromosomal aberration; Genetic mapping; Multiple; Pathogenesis; Chromosome A3; Mitochondrial DNA; Genetic determinism; Genetic disease; Autosomal character; Genetic linkage; Deletion; Limb girdle muscular dystrophy; Genetics; Dominant character; Locus; Autosomal Dominant Limb-Girdle Muscular Dystrophy
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2009.235

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 ( θ =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.