title: LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.
abstract: The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.
authors.affiliation: Division of Medical Genetics, Departments of Medicine and Genetics, University of Leicester, Leicester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Shackleton
authors.forename: D J
authors.initials: DJ
authors.lastname: Lloyd
authors.forename: S N
authors.initials: SN
authors.lastname: Jackson
authors.forename: R
authors.initials: R
authors.lastname: Evans
authors.forename: M F
authors.initials: MF
authors.lastname: Niermeijer
authors.forename: B M
authors.initials: BM
authors.lastname: Singh
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.forename: G
authors.initials: G
authors.lastname: Brabant
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: P N
authors.initials: PN
authors.lastname: Durrington
authors.forename: S
authors.initials: S
authors.lastname: Gregory
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: R C
authors.initials: RC
authors.lastname: Trembath
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A; D034882:Lamins; D008060:Lipodystrophy / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D005819:Genetic Markers; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins