Single-nucleotide polymorphisms of the nuclear lamina proteome

Familial partial lipodystrophy (FPLD) has been shown to be due to mutations in the LMNA gene encoding nuclear lamins A and C, indicating that defectiv e structure of the nuclear envelope can produce this unique phenotype. Some patients with inherited partial lipodystrophy have normal LMNA coding, pro moter, and 3 ' -untranslated region sequences. This suggests that the FPLD phenotype is genetically heterogeneous. Among the candidate genes to consid er for the non-LMNA-associated forms of FPLD are other components of the in ner 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, respective ly. We found no putative disease mutations in any of these proteins in subj ects with non-LMNA FPLD, but, through the screening of diseased and normal subjects, we identified several single-nucleotide polymorphisms (SNPs); spe cifically, five SNPs in LMNB1 and four SNPs in LBR. The LMNB2 gene was mono morphic in screening experiments. We conclude that mutations in other const ituent proteins of the nuclear envelope are not present in subjects with no n-LMNA-associated FPLD. However, the identification of amplification primer s and SNPs provides tools to investigate these proteins for their associati on with other phenotypes.