Title | Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Braun, DA, Schueler, M, Halbritter, J, Gee, HYung, Porath, JD, Lawson, JA, Airik, R, Shril, S, Allen, SJ, Stein, D, Kindy, AAl, Beck, BB, Cengiz, N, Moorani, KN, Ozaltin, F, Hashmi, S, Sayer, JA, Bockenhauer, D, Soliman, NA, Otto, EA, Lifton, RP, Hildebrandt, F |
Journal | Kidney Int |
Volume | 89 |
Issue | 2 |
Pagination | 468-475 |
Date Published | 2016 Feb |
ISSN | 1523-1755 |
Keywords | Age of Onset, Cohort Studies, DNA Mutational Analysis, Exome, Humans, Kidney Diseases, Cystic, Renal Insufficiency, Chronic |
Abstract | Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes. |
DOI | 10.1038/ki.2015.317 |
Alternate Journal | Kidney Int. |
PubMed ID | 26489029 |
PubMed Central ID | PMC4840095 |
Grant List | 5U54HG006504 / HG / NHGRI NIH HHS / United States DK1068306 / DK / NIDDK NIH HHS / United States UM1 HG006504 / HG / NHGRI NIH HHS / United States UL1 TR001863 / TR / NCATS NIH HHS / United States P30 DK079310 / DK / NIDDK NIH HHS / United States K99 DK099434 / DK / NIDDK NIH HHS / United States DK099434 / DK / NIDDK NIH HHS / United States U54 HG006504 / HG / NHGRI NIH HHS / United States R01 DK068306 / DK / NIDDK NIH HHS / United States R00 DK099434 / DK / NIDDK NIH HHS / United States DK064614 / DK / NIDDK NIH HHS / United States R01 DK064614 / DK / NIDDK NIH HHS / United States DK1069274 / DK / NIDDK NIH HHS / United States |