Bardet–Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by obesity, mental impairment, rod-cone dystrophy, polydactyly, male hypogonadism, and renal abnormalities. This disorder is caused by mutations in BBS1-21. Alström syndrome (AS), caused solely by mutations in ALMS1, is another genetic obesity syndrome clinically similar to BBS. We previously conducted the first nationwide survey of BBS in Japan and found four patients with genetically definite BBS. In this study, exome analyses were performed on new patients whose symptoms fulfilled the diagnostic criteria for BBS. We identified one reported heterozygous mutation in BBS1 (p.R429*) in one patient, two novel mutations (p.L493R and p.H719Y) in BBS20 in a second patient, and one novel mutation (p.Q920*) and one reported mutation (p.R2928*) in ALMS1 in a third patient, who was subsequently diagnosed with AS. The first patient with BBS was previously considered to have digenic heterozygous mutations in BBS1 and BBS4. RT-PCR and long-range genomic PCR analyses identified a new heterozygous mutation in BBS1, the deletion of exons 10 and 11. Thus, this patient was compound heterozygous for mutations in BBS1. Many studies have described digenic heterozygous mutations in BBS. However, undetected mutations might have existed in either one of the mutated genes.

Bardet–Biedl综合征（BBS）是一种罕见的常染色体隐性遗传疾病，其特征在于肥胖，精神障碍，杆锥营养不良，多发性，男性性腺功能低下和肾脏异常。这种疾病是由BBS1-21中的突变引起的。Alström综合征（AS）仅由ALMS1突变引起，是另一种与BBS临床相似的遗传性肥胖综合征。我们之前曾在日本进行过首次BBS全国性调查，结果发现了4例遗传定性BBS患者。在这项研究中，对症状符合BBS诊断标准的新患者进行了外显子组分析。我们确定了一个报告杂合突变在BBS1在一个患者（p.R429 *），两个新的突变（p.L493R和p.H719Y）BBS20在第二例患者中，第三例患者的ALMS1中有一个新突变（p.Q920 *）和一个报告的突变（p.R2928 *），随后被诊断为AS。与BBS第一个病人是以前被认为有digenic杂合突变BBS1和BBS4。RT-PCR和远距离基因组PCR分析鉴定在一个新的杂合突变BBS1，外显子10和11的删除因此，该患者是在突变的复合杂BBS1。许多研究描述了BBS中的双基因杂合突变。但是，在任一突变基因中都可能存在未检测到的突变。