Article Text

Original article
Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel
  1. Mohamed H Al-Hamed1,
  2. Wesam Kurdi2,
  3. Nada Alsahan2,
  4. Zainab Alabdullah3,
  5. Rania Abudraz2,
  6. Maha Tulbah2,
  7. Maha Alnemer2,
  8. Rubina Khan2,
  9. Haya Al-Jurayb1,
  10. Ahmed Alahmed1,
  11. Asma I Tahir1,
  12. Dania Khalil1,
  13. Noel Edwards4,
  14. Basma Al Abdulaziz5,
  15. Faisal S Binhumaid1,
  16. Salma Majid1,
  17. Tariq Faquih5,
  18. Mohamed El-Kalioby5,
  19. Mohamed Abouelhoda1,5,
  20. Nada Altassan1,5,
  21. Dorota Monies1,5,
  22. Brian Meyer1,5,
  23. John A Sayer4,
  24. Mamdouh Albaqumi1,6
  1. 1Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
  2. 2Obstetrics and Gynecology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
  3. 3Obstetrics & Gynecology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
  4. 4Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK
  5. 5Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
  6. 6Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
  1. Correspondence to Dr John A Sayer, Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK; John.sayer{at}ncl.ac.uk

Abstract

Background Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease.

Methods To define the phenotype and genotype of cystic kidney disease in fetuses and neonates, we correlated antenatal ultrasound examination and postnatal renal ultrasound examination with targeted exon sequencing, using a renal gene panel. A cohort of 44 families in whom antenatal renal ultrasound scanning findings in affected cases included bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys was investigated.

Results In this cohort, disease phenotypes were severe with 36 cases of stillbirth or perinatal death. Extra renal malformations, including encephalocele, polydactyly and heart malformations, consistent with ciliopathy phenotypes, were frequently detected. Renal gene panel testing identified causative mutations in 21 out of 34 families (62%), where patient and parental DNA was available. In the remaining 10 families, where only parental DNA was available, 7 inferred causative mutations were found. Together, mutations were found in 12 different genes with a total of 13 novel pathogenic variants, including an inferred novel variant in NEK8. Mutations in CC2D2A were the most common cause of an antenatal cystic kidney disease and a suspected ciliopathy in our cohort.

Conclusions In families with ciliopathy phenotypes, mutational analysis using a targeted renal gene panel allows a rapid molecular diagnosis and provides important information for patients, parents and their physicians.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

View Full Text

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.