Beijing Key Laboratory for Genetics of Birth Defects, Key Laboratory of Major Diseases in Children of Ministry of Education, Center for Medical Genetics, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
Beijing Key Laboratory for Chronic Renal Disease and Blood Purification, Key Laboratory of Major Diseases in Children of Ministry of Education; Nephrology Department, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
Sci China Life Sci. 2017 Jul;60(7):739-745. doi: 10.1007/s11427-017-9085-7. Epub 2017 Jun 14.
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity, developmental delay, and renal defects. At least 21 candidate BBS-associated genes (BBS1-19, NPHP1, and IFT172) have previously been identified, and all of them play important roles in ciliary function. Here, we collected a BBS pedigree with four members and performed whole-exome sequencing on the proband. The variants were analyzed and evaluated to confirm their pathogenicity. We found compound heterozygous variants (c.1192C>T, p.Q398* and c.1175C>T, p.T392M) in MKKS in both the siblings, and these were likely to be pathogenic variants. We also found a missense variant (c.2029G>C, p.E677Q) in NPHP1 and a missense variant (c.2470C>T, p.R824C) in BBS9 in the proband only, which are variants of uncertain significance. The compound heterozygous variants were probably responsible for the BBS phenotype in this Chinese pedigree and the missense mutations in NPHP1 and BBS9 might contribute to the mutation load.
Bardet-Biedl 综合征（BBS）是一种遗传异质性疾病，其特征为视网膜营养不良、多指（趾）畸形、肥胖、发育迟缓以及肾脏缺陷。先前已经鉴定出至少 21 个候选 BBS 相关基因（BBS1-19、NPHP1 和 IFT172），所有这些基因在纤毛功能中都发挥着重要作用。在这里，我们收集了一个有四个成员的 BBS 家系，并对先证者进行了全外显子组测序。对变体进行了分析和评估，以确认其致病性。我们在两个兄弟姐妹中均发现了 MKKS 中的复合杂合变体（c.1192C>T，p.Q398*和 c.1175C>T，p.T392M），这些可能是致病性变体。我们还在先证者中仅发现了 NPHP1 中的错义变体（c.2029G>C，p.E677Q）和 BBS9 中的错义变体（c.2470C>T，p.R824C），这些是意义未明的变体。复合杂合变体可能是导致这个中国家系中 BBS 表型的原因，而 NPHP1 和 BBS9 中的错义突变可能导致了突变负荷的增加。
