Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

Daniela A. Braun, Markus Schueler, Jan Halbritter, Heon Yung Gee, Jonathan D. Porath, Jennifer A. Lawson, Rannar Airik, Shirlee Shril, Susan J. Allen, Deborah Stein, Adila Al Kindy, Bodo B. Beck, Nurcan Cengiz, Khemchand N. Moorani, Fatih Ozaltin, Seema Hashmi, John A. Sayer, Detlef Bockenhauer, Neveen A. Soliman, Edgar A. OttoRichard P. Lifton, Friedhelm Hildebrandt

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)468-475
Number of pages8
JournalKidney International
Volume89
Issue number2
DOIs
Publication statusPublished - 2016 Feb 1

All Science Journal Classification (ASJC) codes

  • Nephrology

Fingerprint Dive into the research topics of 'Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity'. Together they form a unique fingerprint.

  • Cite this

    Braun, D. A., Schueler, M., Halbritter, J., Gee, H. Y., Porath, J. D., Lawson, J. A., Airik, R., Shril, S., Allen, S. J., Stein, D., Al Kindy, A., Beck, B. B., Cengiz, N., Moorani, K. N., Ozaltin, F., Hashmi, S., Sayer, J. A., Bockenhauer, D., Soliman, N. A., ... Hildebrandt, F. (2016). Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity. Kidney International, 89(2), 468-475. https://doi.org/10.1038/ki.2015.317