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

被引：73

作者：

Bekheirnia, Mir Reza ^{[1
,2
,3
,4
]}

Bekheirnia, Nasim ^{[1
,2
,4
]}

Bainbridge, Matthew N. ^{[5
]}

Gu, Shen ^{[1
]}

Akdemir, Zeynep Hande Coban ^{[1
]}

Gambin, Tomek ^{[1
]}

Janzen, Nicolette K. ^{[3
,4
]}

Jhangiani, Shalini N. ^{[5
]}

Muzny, Donna M. ^{[5
]}

Michael, Mini ^{[4
,6
]}

Brewer, Eileen D. ^{[4
,6
]}

Elenberg, Ewa ^{[4
,6
]}

Kale, Arundhati S. ^{[4
,6
]}

Riley, Alyssa A. ^{[4
,6
]}

Swartz, Sarah J. ^{[4
,6
]}

Scott, Daryl A. ^{[1
,4
]}

Yang, Yaping ^{[1
]}

Srivaths, Poyyapakkam R. ^{[4
,6
]}

Wenderfer, Scott E. ^{[4
,6
]}

Bodurtha, Joann ^{[7
]}

Applegate, Carolyn D. ^{[7
]}

Velinov, Milen ^{[8
]}

Myers, Angela ^{[9
]}

Borovik, Lior

Craigen, William J. ^{[1
]}

Hanchard, Neil A. ^{[1
,4
]}

Rosenfeld, Jill A. ^{[1
]}

Lewis, Richard Alan ^{[1
,4
,10
]}

Gonzales, Edmond T. ^{[3
,4
]}

Gibbs, Richard A. ^{[1
,5
]}

Belmont, John W. ^{[1
,4
]}

Roth, David R. ^{[3
,4
]}

Eng, Christine ^{[1
]}

Braun, Michael C. ^{[4
,6
]}

Lupski, James R. ^{[1
,4
,5
,11
]}

Lamb, Dolores J. ^{[2
,3
,12
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Baylor Coll Med, Ctr Reprod Med, Houston, TX 77030 USA

[3] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA

[4] Texas Childrens Hosp, Houston, TX 77030 USA

[5] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[6] Baylor Coll Med, Dept Pediat, Renal Sect, Houston, TX 77030 USA

[7] Johns Hopkins Childrens Ctr, Inst Med Genet, Baltimore, MD USA

[8] NYS Inst Basic Res Dev Disabil, Staten Isl, NY USA

[9] Sanford Childrens Hosp, Sioux Falls, SD USA

[10] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA

[11] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[12] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

GENETICS IN MEDICINE | 2017年 / 19卷 / 04期

关键词：

CAKUT; WES; FOXPI; PAX2; HNFIB; CAT EYE SYNDROME; NUMBER VARIATION DETECTION; DE-NOVO MUTATIONS; PHENOTYPIC VARIABILITY; MEDICAL GENETICS; AMERICAN-COLLEGE; FOXP1; VARIANTS; GUIDELINES; STANDARDS;

D O I：

10.1038/gim.2016.131

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: To investigate the utility ofwhole-exome sequencing (WES) to define a molecular diagnosis for patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). Methods: 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). Results: In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNFIB, and EYA I. 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 FOXPI among the 62 families with CAKUT. The clinical database of the Baylor Miraca Genetics laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXPI were identified. Six of these eight individuals with FOXPI SNVs have syndromic urinary tract defects, implicating this gene in urinary tract development. Conclusion: We conclude that WES can be used to identify molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.

引用

页码：412 / 420

页数：9

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