Whole-exome sequencing in a Japanese pedigree implicates a rare non-synonymous single-nucleotide variant in BEST3 as a candidate for mandibular prognathism.
Whole-exome sequencing in a Japanese pedigree implicates a rare non-synonymous single-nucleotide variant in BEST3 as a candidate for mandibular prognathism.
复制标题
DOI：
10.1016/j.bone.2019.03.004
复制
发表时间：
2019-05
期刊：
影响因子：
4.1
通讯作者：
T. Kajii;A. Oka;F. Saito;J. Mitsui;J. Iida
中科院分区：
文献类型：
--
作者：
T. Kajii;A. Oka;F. Saito;J. Mitsui;J. Iida
下颌前突是一种面部畸形的表型，在世界各地的人群中都可以看到，但在东亚人群中发病率较高。五项全基因组非参数连锁分析和一项全基因组关联研究显示了不一致的结果，以确定表型的易感性位点。为了探索与下颌前突症相关的变异，我们对一个日本家系进行了全外显子组测序。家谱确定为下颌前突症。该谱系由4代15个个体组成。选择4个跨2代的受影响个体和5个未受影响个体进行全外显子组测序。在所有4例患者中均检测到fubash3b、OR6M1、OR8D4、OR8B4和best3基因的5个非同义单核苷酸变异（SNVs），但在5例未受影响的患者中均未检测到。best3基因Chr12（GRCh37）的非同义SNV:g。70048878 g > T, NM_032735.2: c。1816C >a, p.（L606I）被鉴定为罕见的错义变异。best3位于染色体12q15上，编码besstrophin家族阴离子通道中的besstrophin 3。fubash3b、OR6M1、OR8D4和or8b4的其他4个非同义snv不被认为是下颌前突的合理候选者。我们的全外显子组测序表明，在日本谱系中，best3的罕见非同义SNV可能是下颌前突症的候选基因。
Mandibular prognathism is a phenotype of facial deformity seen in populations around the world, but with higher incidence among East Asian populations. Five genome-wide nonparametric linkage analyses and a genome-wide association study to identify susceptibility loci of the phenotype have shown inconsistent results. To explore variants related to mandibular prognathism, we undertook whole-exome sequencing in a Japanese pedigree. The pedigree was ascertained as mandibular prognathism. The pedigree comprised 15 individuals from 4 generations. Four affected individuals across 2 generations and 5 unaffected individuals were chosen for whole-exome sequencing. Five non-synonymous single-nucleotide variants (SNVs) ofUBASH3B,OR6M1,OR8D4,OR8B4, andBEST3genes were detected in all 4 affected individuals, but in none of the 5 unaffected individuals. A non-synonymous SNV of theBEST3gene, Chr12(GRCh37):g.70048878G>T, NM_032735.2:c.1816C>A, p.(L606I), was identified as rare missense variant.BEST3is located on chromosome 12q15 and encodes bestrophin 3 from the bestrophin family of anion channels. The 4 other non-synonymous SNVs ofUBASH3B,OR6M1,OR8D4, andOR8B4were not considered plausible candidates for mandibular prognathism. Our whole-exome sequencing implicates a rare non-synonymous SNV ofBEST3as a candidate for mandibular prognathism in the Japanese pedigree.