|Title||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.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Bekheirnia, MReza, Bekheirnia, N, Bainbridge, MN, Gu, S, Akdemir, ZHande Coba, 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, RAlan, Gonzales, ET, Gibbs, RA, Belmont, JW, Roth, DR, Eng, C, Braun, MC, Lupski, JR, Lamb, DJ|
|Date Published||2017 Apr|
|Keywords||Adolescent, Child, Child, Preschool, DNA Copy Number Variations, Exome Sequencing, Female, Forkhead Transcription Factors, Genetic Predisposition to Disease, Hepatocyte Nuclear Factor 1-beta, Humans, Infant, Intracellular Signaling Peptides and Proteins, Male, Nuclear Proteins, PAX2 Transcription Factor, Pedigree, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatases, Repressor Proteins, Urogenital Abnormalities, Vesico-Ureteral Reflux, Young Adult|
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.
|Alternate Journal||Genet Med|
|PubMed Central ID||PMC5362362|
|Grant List||U54 HG006542 / HG / NHGRI NIH HHS / United States |
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 DK078121 / DK / NIDDK NIH HHS / United States
K12 DK083014 / DK / NIDDK NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States