RT Journal Article
SR Electronic
T1 Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 2348
OP 2361
DO 10.1681/ASN.2017121265
VO 29
IS 9
A1 van der Ven, Amelie T.
A1 Connaughton, Dervla M.
A1 Ityel, Hadas
A1 Mann, Nina
A1 Nakayama, Makiko
A1 Chen, Jing
A1 Vivante, Asaf
A1 Hwang, Daw-yang
A1 Schulz, Julian
A1 Braun, Daniela A.
A1 Schmidt, Johanna Magdalena
A1 Schapiro, David
A1 Schneider, Ronen
A1 Warejko, Jillian K.
A1 Daga, Ankana
A1 Majmundar, Amar J.
A1 Tan, Weizhen
A1 Jobst-Schwan, Tilman
A1 Hermle, Tobias
A1 Widmeier, Eugen
A1 Ashraf, Shazia
A1 Amar, Ali
A1 Hoogstraaten, Charlotte A.
A1 Hugo, Hannah
A1 Kitzler, Thomas M.
A1 Kause, Franziska
A1 Kolvenbach, Caroline M.
A1 Dai, Rufeng
A1 Spaneas, Leslie
A1 Amann, Kassaundra
A1 Stein, Deborah R.
A1 Baum, Michelle A.
A1 Somers, Michael J.G.
A1 Rodig, Nancy M.
A1 Ferguson, Michael A.
A1 Traum, Avram Z.
A1 Daouk, Ghaleb H.
A1 Bogdanović, Radovan
A1 Stajić, Natasa
A1 Soliman, Neveen A.
A1 Kari, Jameela A.
A1 El Desoky, Sherif
A1 Fathy, Hanan M.
A1 Milosevic, Danko
A1 Al-Saffar, Muna
A1 Awad, Hazem S.
A1 Eid, Loai A.
A1 Selvin, Aravind
A1 Senguttuvan, Prabha
A1 Sanna-Cherchi, Simone
A1 Rehm, Heidi L.
A1 MacArthur, Daniel G.
A1 Lek, Monkol
A1 Laricchia, Kristen M.
A1 Wilson, Michael W.
A1 Mane, Shrikant M.
A1 Lifton, Richard P.
A1 Lee, Richard S.
A1 Bauer, Stuart B.
A1 Lu, Weining
A1 Reutter, Heiko M.
A1 Tasic, Velibor
A1 Shril, Shirlee
A1 Hildebrandt, Friedhelm
YR 2018
UL http://jasn.asnjournals.org/content/29/9/2348.abstract
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.