Whole-exome sequencing identified compound heterozygous variants in MMKS in a Chinese pedigree with Bardet-Biedl syndrome

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 r...

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Veröffentlicht in:Science China. Life sciences 2017-07, Vol.60 (7), p.739-745
Hauptverfasser: Qi, Zhan, Shen, Ying, Fu, Qian, Li, Wei, Yang, Wei, Xu, Wenshan, Chu, Ping, Zhang, Yaxin, Wang, Hui
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container_title Science China. Life sciences
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Shen, Ying
Fu, Qian
Li, Wei
Yang, Wei
Xu, Wenshan
Chu, Ping
Zhang, Yaxin
Wang, Hui
description 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.
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Life sciences</title><addtitle>Sci. China Life Sci</addtitle><addtitle>Sci China Life Sci</addtitle><description>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. 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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.</abstract><cop>Beijing</cop><pub>Science China Press</pub><pmid>28624958</pmid><doi>10.1007/s11427-017-9085-7</doi><tpages>7</tpages></addata></record>
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subjects Adaptor Proteins, Signal Transducing - genetics
Bardet-Biedl syndrome
Bardet-Biedl Syndrome - genetics
BBS
Biomedical and Life Sciences
Child
Exome
Female
Group II Chaperonins - genetics
Heterozygote
High-Throughput Nucleotide Sequencing
Humans
Kidneys
Life Sciences
Membrane Proteins - genetics
Missense mutation
MKKS protein
Mutation
Neoplasm Proteins - genetics
Pathogenicity
Pedigree
Polydactyly
Polymorphism, Single Nucleotide
Research Paper
Retina
Retinal degeneration
Siblings
全基因组测序
复合
家系
突变
综合征
营养不良
遗传异质性
title Whole-exome sequencing identified compound heterozygous variants in MMKS in a Chinese pedigree with Bardet-Biedl syndrome
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