Kidney Week

Abstract: SA-PO566

Whole Exome Sequencing Identifies the Causative Mutation in 50% of Families with Adult-Onset CKD

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Connaughton, Dervla M., Boston Children's Hospital, Boston, United States

Dervla M. Connaughton,

• Kennedy, Claire, Beaumont Hospital, Dublin 9, Ireland

Claire Kennedy,

• Shril, Shirlee, Boston Children's Hospital, Boston, Massachusetts, United States

Shirlee Shril,

• van der Ven, Amelie, Boston Children's Hospital, Boston, Massachusetts, United States

Amelie van der Ven,

• Ityel, Hadas, Boston Children's Hospital, Boston, Massachusetts, United States

Hadas Ityel,

• Mann, Nina, Boston Children's Hospital, Boston, Massachusetts, United States

Nina Mann,

• Mane, Shrikant M., Yale University School of Medicine, New Haven, Massachusetts, United States

Shrikant M. Mane,

• Little, Mark Alan, Tallaght Hospital, Dublin, Ireland

Mark Alan Little,

• Conlon, Peter J., Beaumont Hospital, Dublin 9, Ireland

Peter J. Conlon,

• Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Friedhelm Hildebrandt,

Background

Over 250 monogenic causes of chronic kidney disease (CKD) have been identified (Nat Rev Nephrol 12:133, 2016), mostly in pediatric populations. However, the frequency of monogenic causation in adult-onset CKD has not been extensively studied.

Methods

We conducted whole exome sequencing (WES) in 16 Irish families (27 cases) with CKD. Selection criteria were: A positive family history of CKD (n=12 families) and/or history of extra-renal disease manifestations (n=8 families). Individuals with autosomal dominant polycystic kidney disease or Alport’s syndrome were excluded.

Results

WES identified a causative mutation in one of 250 known monogenic CKD genes in 50% of families (n=8/16 families, 12 individuals). Six of the 8 families had no prior diagnosis of the cause of CKD. The 8 families in whom a causative mutation was identified included nephronophthisis (n=4, IFT140, NPHP1, BBS9, DYNC2H1), autosomal recessive polycystic kidney disease (n=1, PKHD1), congenital abnormalities of the kidneys and urinary tract (n=1, PAX2), Lowe’s syndrome (n=1, OCRL) and interstitial nephritis (n=1, FAN1). In 3 families, in whom known CKD genes were excluded, 3 different potential novel candidate genes were identified.

Conclusion

This study establish that WES can detect specific causative mutations in 50% of families with adult-onset CKD. Furthermore, WES allows the identification of novel candidate genes. WES is therefore an important diagnostic tool to establish an etiologic diagnosis in an adult-onset CKD.

Funding

• Other NIH Support