PT  - JOURNAL ARTICLE
AU  - van der Ven, Amelie T.
AU  - Connaughton, Dervla M.
AU  - Ityel, Hadas
AU  - Mann, Nina
AU  - Nakayama, Makiko
AU  - Chen, Jing
AU  - Vivante, Asaf
AU  - Hwang, Daw-yang
AU  - Schulz, Julian
AU  - Braun, Daniela A.
AU  - Schmidt, Johanna Magdalena
AU  - Schapiro, David
AU  - Schneider, Ronen
AU  - Warejko, Jillian K.
AU  - Daga, Ankana
AU  - Majmundar, Amar J.
AU  - Tan, Weizhen
AU  - Jobst-Schwan, Tilman
AU  - Hermle, Tobias
AU  - Widmeier, Eugen
AU  - Ashraf, Shazia
AU  - Amar, Ali
AU  - Hoogstraaten, Charlotte A.
AU  - Hugo, Hannah
AU  - Kitzler, Thomas M.
AU  - Kause, Franziska
AU  - Kolvenbach, Caroline M.
AU  - Dai, Rufeng
AU  - Spaneas, Leslie
AU  - Amann, Kassaundra
AU  - Stein, Deborah R.
AU  - Baum, Michelle A.
AU  - Somers, Michael J.G.
AU  - Rodig, Nancy M.
AU  - Ferguson, Michael A.
AU  - Traum, Avram Z.
AU  - Daouk, Ghaleb H.
AU  - Bogdanović, Radovan
AU  - Stajić, Natasa
AU  - Soliman, Neveen A.
AU  - Kari, Jameela A.
AU  - El Desoky, Sherif
AU  - Fathy, Hanan M.
AU  - Milosevic, Danko
AU  - Al-Saffar, Muna
AU  - Awad, Hazem S.
AU  - Eid, Loai A.
AU  - Selvin, Aravind
AU  - Senguttuvan, Prabha
AU  - Sanna-Cherchi, Simone
AU  - Rehm, Heidi L.
AU  - MacArthur, Daniel G.
AU  - Lek, Monkol
AU  - Laricchia, Kristen M.
AU  - Wilson, Michael W.
AU  - Mane, Shrikant M.
AU  - Lifton, Richard P.
AU  - Lee, Richard S.
AU  - Bauer, Stuart B.
AU  - Lu, Weining
AU  - Reutter, Heiko M.
AU  - Tasic, Velibor
AU  - Shril, Shirlee
AU  - Hildebrandt, Friedhelm
TI  - Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract
AID  - 10.1681/ASN.2017121265
DP  - 2018 Sep 01
TA  - Journal of the American Society of Nephrology
PG  - 2348--2361
VI  - 29
IP  - 9
4099  - http://jasn.asnjournals.org/content/29/9/2348.short
4100  - http://jasn.asnjournals.org/content/29/9/2348.full
SO  - J. Am. Soc. Nephrol.2018 Sep 01; 29
AB  - Background Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of kidney disease in the first three decades of life. Previous gene panel studies showed monogenic causation in up to 12% of patients with CAKUT.Methods We applied whole-exome sequencing to analyze the genotypes of individuals from 232 families with CAKUT, evaluating for mutations in single genes known to cause human CAKUT and genes known to cause CAKUT in mice. In consanguineous or multiplex families, we additionally performed a search for novel monogenic causes of CAKUT.Results In 29 families (13%), we detected a causative mutation in a known gene for isolated or syndromic CAKUT that sufficiently explained the patient’s CAKUT phenotype. In three families (1%), we detected a mutation in a gene reported to cause a phenocopy of CAKUT. In 15 of 155 families with isolated CAKUT, we detected deleterious mutations in syndromic CAKUT genes. Our additional search for novel monogenic causes of CAKUT in consanguineous and multiplex families revealed a potential single, novel monogenic CAKUT gene in 19 of 232 families (8%).Conclusions We identified monogenic mutations in a known human CAKUT gene or CAKUT phenocopy gene as the cause of disease in 14% of the CAKUT families in this study. Whole-exome sequencing provides an etiologic diagnosis in a high fraction of patients with CAKUT and will provide a new basis for the mechanistic understanding of CAKUT.