title: Autosomal dominant Brody disease cosegregates with a chromosomal (2;7)(p11.2;p12.1) translocation in an Italian family.
abstract: Brody disease is a rare muscle disorder characterized by exercise-induced impairment in muscle relaxation, due to a markedly reduced influx of calcium ions in the sarcoplasmic reticulum. A subset of autosomal recessive families harbour mutations in the ATP2A1 gene, encoding the fast-twitch skeletal muscle sarcoplasmic reticulum Ca(2+) ATPase (SERCA1). Rare autosomal dominant families have been described, in which ATP2A1 was excluded as the causative gene, further supporting genetic heterogeneity. We report four individuals from a three-generation Italian family with a clinical phenotype of Brody disease, in which linkage analysis excluded ATP2A1 as the responsible gene. The disease cosegregates in an autosomal dominant fashion with an apparently balanced constitutional chromosome translocation (2;7)(p11.2;p12.1), suggesting a causal relationship between the rearrangement and the phenotype. FISH analysis using YAC and PAC clones as probes refined the breakpoint regions to genomic segments of about 164 and 120 kb, respectively, providing a possible clue to pinpoint the location of a novel gene responsible for this rare muscle disorder.
authors.affiliation: IRCCS CSS, San Giovanni Rotondo and CSS Mendel, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Caterina
authors.initials: C
authors.lastname: Ceccarini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Sinibaldi
authors.forename: Viviana
authors.initials: V
authors.lastname: Caputo
authors.forename: Pietro
authors.initials: P
authors.lastname: Cavalli
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000328:Adult; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002874:Chromosome Mapping; D020223:Chromosome Painting; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020967:Myotonic Disorders / Q000235:genetics*; D010375:Pedigree; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506943:ATP2A1 protein, human; D000252:Calcium-Transporting ATPases