title: Single-nucleotide polymorphisms of the nuclear lamina proteome.
abstract: Familial partial lipodystrophy (FPLD) has been shown to be due to mutations in the LMNA gene encoding nuclear lamins A and C, indicating that defective structure of the nuclear envelope can produce this unique phenotype. Some patients with inherited partial lipodystrophy have normal LMNA coding, promoter, and 3'-untranslated region sequences. This suggests that the FPLD phenotype is genetically heterogeneous. Among the candidate genes to consider for the non-LMNA-associated forms of FPLD are other components of the inner nuclear membrane, such as lamin B1 and B2 and the lamin B receptor. We developed amplification primers for the coding regions of LMNB1, LMNB2, and LBR, which encode lamin B1, lamin B2, and the lamin B receptor, respectively. We found no putative disease mutations in any of these proteins in subjects with non-LMNA FPLD, but, through the screening of diseased and normal subjects, we identified several single-nucleotide polymorphisms (SNPs); specifically, five SNPs in LMNB1 and four SNPs in LBR. The LMNB2 gene was monomorphic in screening experiments. We conclude that mutations in other constituent proteins of the nuclear envelope are not present in subjects with non-LMNA-associated FPLD. However, the identification of amplification primers and SNPs provides tools to investigate these proteins for their association with other phenotypes.
authors.affiliation: Blackburn Cardiovascular Genetics Laboratory, John P Robarts Research Institute, London, Ontario, Canada. robert.hegele@rri.on.ca
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
authors.forename: J
authors.initials: J
authors.lastname: Yuen
authors.forename: H
authors.initials: H
authors.lastname: Cao
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D034921:Lamin Type B; D034882:Lamins; D008060:Lipodystrophy / Q000235:genetics*; D009685:Nuclear Envelope / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020543:Proteome / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D000097682:Lamin B Receptor
chemical_list: D017931:DNA Primers; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D020543:Proteome; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor