title: Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.
abstract: Emery-Dreifuss muscular dystrophy (EMD) is a condition characterized by the clinical triad of early-onset contractures, progressive weakness in humeroperoneal muscles, and cardiomyopathy with conduction block. The disease was described for the first time as an X-linked muscular dystrophy, but autosomal dominant and autosomal recessive forms were reported. The genes for X-linked EMD and autosomal dominant EMD (AD-EMD) were identified. We report here that heterozygote mutations in LMNA, the gene for AD-EMD, may cause diverse phenotypes ranging from typical EMD to no phenotypic effect. Our results show that LMNA mutations are also responsible for the recessive form of the disease. Our results give further support to the notion that different genetic forms of EMD have a common pathophysiological background. The distribution of the mutations in AD-EMD patients (in the tail and in the 2A rod domain) suggests that unique interactions between lamin A/C and other nuclear components exist that have an important role in cardiac and skeletal muscle function.
authors.affiliation: Institute of Genetics, Biochemistry and Evolution-Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Raffaele Di Barletta
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: G
authors.initials: G
authors.lastname: Galluzzi
authors.forename: P
authors.initials: P
authors.lastname: Tonali
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.forename: A
authors.initials: A
authors.lastname: Romorini
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: K H
authors.initials: KH
authors.lastname: Orstavik
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: C
authors.initials: C
authors.lastname: Trevisan
authors.forename: V
authors.initials: V
authors.lastname: Biancalana
authors.forename: I
authors.initials: I
authors.lastname: Housmanowa-Petrusewicz
authors.forename: S
authors.initials: S
authors.lastname: Bione
authors.forename: R
authors.initials: R
authors.lastname: Ricotti
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: D
authors.initials: D
authors.lastname: Toniolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007797:Laminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary
chemical_list: D007797:Laminin; C084098:laminin A