title: A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H.
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.
authors.affiliation: Department of evolutive age, Medical Genetics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bisceglia
authors.forename: Stefano
authors.initials: S
authors.lastname: Zoccolella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Torraco
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Piemontese
authors.forename: Rosa
authors.initials: R
authors.lastname: Dell'Aglio
authors.forename: Angela
authors.initials: A
authors.lastname: Amati
authors.forename: Patrizia
authors.initials: P
authors.lastname: De Bonis
authors.forename: Lucia
authors.initials: L
authors.lastname: Artuso
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Serlenga
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005190:Family; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult