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

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Braun D. A., Schueler M., Halbritter J., Gee H. Y., Porath J. D., Lawson J. A., ...Daha Fazla

KIDNEY INTERNATIONAL, cilt.89, sa.2, ss.468-475, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 89 Sayı: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1038/ki.2015.317
  • Dergi Adı: KIDNEY INTERNATIONAL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.468-475
  • Anahtar Kelimeler: chronic kidney disease, genetic kidney disease, pediatric nephrology, LINKAGE ANALYSIS, NEPHRONOPHTHISIS, DISEASE, MECHANISMS, CILIOPATHY, CILIARY, INVS, NEK8
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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, PIASI, INCENP, and RCORI) 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.