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Genet Med. 2017 Apr;19(4):412-420. doi: 10.1038/gim.2016.131. Epub 2016 Sep 22.

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.

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
2
Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas, USA.
3
Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.
4
Texas Children's Hospital, Houston, Texas, USA.
5
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
6
Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
7
Johns Hopkins Children's Center, Institute of Genetic Medicine, Baltimore, Maryland, USA.
8
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
9
Sanford Children's Hospital, Sioux Falls, South Dakota, USA.
10
Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
11
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
12
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.

Abstract

PURPOSE:

To investigate the utility of whole-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, 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. The clinical database of the Baylor Miraca Genetics laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these eight individuals with FOXP1 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.Genet Med 19 4, 412-420.

PMID:
27657687
PMCID:
PMC5362362
DOI:
10.1038/gim.2016.131
[Indexed for MEDLINE]
Free PMC Article

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