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.

Mutations in the LMNA gene, which encodes nuclear lamins A and C, underlie both Emery-Dreifuss muscular dystrophy (EMD2) and Dunnigan-type familial partial lipodystrophy (FPLD). This indicates that one gene can cause different phenotypes characterized by tissue degeneration. The gene for one form of Berardinelli-Seip-type congenital total lipodystrophy (BSCL) has been mapped to chromosome 9q34. Based on the observation that one gene caused both FPLD and EMD2, we considered that a known gene for muscular dystrophy at or near the BSCL locus on chromosome 9q would be an appropriate candidate for BSCL. The gene encoding fukutin, which is mutated in Fukuyama congenital muscular dystrophy has been mapped to 9q31. We thus developed amplification primers for the coding regions of the fukutin gene. We found no putative disease mutations, but through screening of diseased and normal subjects, we identified three novel single nucleotide polymorphisms (SNPs). We conclude that mutations in fukutin are not present in subjects with BSCL. However, the identification of SNPs provides tools to investigate this protein for association with other phenotypes.