Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene.
Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene.
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DOI：
10.1038/gim.2016.131
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Lamb DJ
中科院分区：
文献类型：
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作者：
Bekheirnia MR;Bekheirnia N;Bainbridge MN;Gu S;Coban Akdemir ZH;Gambin T;Janzen NK;Jhangiani SN;Muzny DM;Michael M;Brewer ED;Elenberg E;Kale AS;Riley AA;Swartz SJ;Scott DA;Yang Y;Srivaths PR;Wenderfer SE;Bodurtha J;Applegate CD;Velinov M;Myers A;Borovik L;Craigen WJ;Hanchard NA;Rosenfeld JA;Lewis RA;Gonzales ET;Gibbs RA;Belmont JW;Roth DR;Eng C;Braun MC;Lupski JR;Lamb DJ
探讨全外显子组测序（WES）在临床诊断为先天性肾脏和泌尿道畸形（CAKUT）患者中的分子诊断价值。对62个CAKUT家系进行了WES检查。WES数据分析了35个已知CAKUT基因中的单核苷酸变异（SNV），新候选基因中的有害序列变化，以及潜在的疾病相关拷贝数变异（CNV）。在大约5%的家族中，在PAX2、HNF 1B和EYA 1中鉴定出致病性SNV。在这些家族中观察到的表型扩展了目前对这些基因在CAKUT中作用的理解。还使用两种CNV检测工具鉴定了四种致病性CNV。另外，我们在62个CAKUT家族中发现了FOXP1中的一个有害的新生SNV。查询了临床BMGL实验室数据库，并确定了另外7名在FOXP 1中具有新的新发SNV的无关个体。这8个个体中的6个具有FOXP1 SNV，具有综合征性尿路缺陷，暗示该基因与尿路发育有关。我们的结论是，WES可以用来确定分子病因（SNVs，CNVs）在一个子集的个人与CAKUT。WES还可以帮助识别新的CAKUT基因。
To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis in patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). WES was performed in 62 families with CAKUT. WES data were analyzed for Single Nucleotide Variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs). In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. Database of clinical BMGL laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these 8 individuals with FOXP1 SNVs, have syndromic urinary tract defects, implicating this gene in urinary tract development. We conclude that WES can be used to identify the molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.