title: Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy.
abstract: The etiology of acquired partial lipodystrophy (APL, also called "Barraquer-Simons syndrome") is unknown. Genomic DNA mutations affecting the nuclear lamina protein lamin A cause inherited partial lipodystrophy but are not found in patients with APL. Because it also encodes a nuclear lamina protein (lamin B2) and its genomic structure was recently reannotated, we sequenced LMNB2 as a candidate gene in nine white patients with APL. In four patients, we found three new rare mutations in LMNB2: intron 1 -6G-->T, exon 5 c.643G-->A (p.R215Q; in two patients), and exon 8 c.1218G-->A (p.A407T). The combined frequency of these mutations was 0.222 in the patients with APL, compared with 0.0018 in a multiethnic control sample of 1,100 subjects (P = 2.1 x 10-7) and 0.0045 in a sample of 330 white controls (P = 1.2 x 10-5). These novel heterozygous mutations are the first reported for LMNB2, are the first reported among patients with APL, and indicate how sequencing of a reannotated candidate gene can reveal new disease-associated mutations.
authors.affiliation: Robarts Research Institute, 406-100 Perth Drive, London, Ontario, Canada N6A 5K8. hegele@robarts.ca
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Henian
authors.initials: H
authors.lastname: Cao
authors.forename: Dora M
authors.initials: DM
authors.lastname: Liu
authors.forename: Gary A
authors.initials: GA
authors.lastname: Costain
authors.forename: Valentine
authors.initials: V
authors.lastname: Charlton-Menys
authors.forename: N Wilson
authors.initials: NW
authors.lastname: Rodger
authors.forename: Paul N
authors.initials: PN
authors.lastname: Durrington
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003923:Diabetes Mellitus, Lipoatrophic / Q000235:genetics*; D005260:Female; D006801:Humans; D034921:Lamin Type B / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D034921:Lamin Type B