The Kennedy Center, GI. Landevej 7, Glostrup, Denmark.
Hum Mutat. 2010 Apr;31(4):429-36. doi: 10.1002/humu.21204.
Bardet-Biedl syndrome (BBS) is an autosomal recessive disease characterized by retinal dystrophy, polydactyly, obesity, learning disabilities, renal involvement, and male hypogenitalism. BBS is genetically heterogeneous with mutations of 14 genes, accounting for approximately 70% of cases. Triallelic inheritance has been suggested in about 5% of cases. Forty-nine unrelated BBS patients were screened for mutations by DHPLC analysis in BBS1, BBS2, BBS4, BBS6/MKKS, BBS10, and BBS12. The selected genes either account for more than 5% of the mutational load or are commonly reported in triallelic inheritance. Eight patients with only one or no BBS mutation were further investigated by single nucleotide polymorphism (SNP) analysis. In total, mutations were detected in 44 patients. Twenty percent had two mutations in BBS1, 18% in BBS2, 4% in BBS9, 43% in BBS10, and 2% in BBS12. Five patients were heterozygous for a sequence variation in BBS6/MKKS. We found eight patients with three sequence variations in two genes, which could be explained by triallelic inheritance, by the prevalence of heterozygous carriers or the third sequence variations representing rare polymorphisms. All changes found in a second BBS gene were amino acid substitutions. Genotype-phenotype correlations suggest a milder phenotype for BBS1 compared to BBS2 and BBS10, which we ascribe to the hypomorphic p.Met390Arg-mutation.
Bardet-Biedl 综合征（BBS）是一种常染色体隐性疾病，其特征为视网膜营养不良、多指（趾）畸形、肥胖、学习障碍、肾脏受累和男性性腺功能减退。BBS 遗传异质性较大，有 14 个基因突变，约占 70%的病例。约 5%的病例存在三等位基因遗传。通过 DHPLC 分析在 BBS1、BBS2、BBS4、BBS6/MKKS、BBS10 和 BBS12 中筛选 49 名无关 BBS 患者的突变。选择的基因要么占突变负荷的 5%以上，要么在三等位基因遗传中常见报道。对仅有一个或没有 BBS 突变的 8 名患者进行单核苷酸多态性（SNP）分析。总共在 44 名患者中检测到突变。20%的患者在 BBS1 中有两个突变，18%的患者在 BBS2 中有两个突变，4%的患者在 BBS9 中有两个突变，43%的患者在 BBS10 中有两个突变，2%的患者在 BBS12 中有两个突变。5 名患者 BBS6/MKKS 存在序列变异的杂合性。我们发现 8 名患者在两个基因中有三个序列变异，这可以通过三等位基因遗传、杂合携带者的流行或第三个序列变异代表罕见多态性来解释。在第二个 BBS 基因中发现的所有变化都是氨基酸取代。基因型-表型相关性表明 BBS1 比 BBS2 和 BBS10 的表型更轻微，我们将其归因于功能降低的 p.Met390Arg 突变。
