title: Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Mohamed H
authors: MH
authors: Al-Hamed
authors: Obstetrics and Gynecology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Wesam
authors: W
authors: Kurdi
authors: Obstetrics and Gynecology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Nada
authors: N
authors: Alsahan
authors: Obstetrics & Gynecology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors: Zainab
authors: Z
authors: Alabdullah
authors: Obstetrics and Gynecology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Rania
authors: R
authors: Abudraz
authors: Obstetrics and Gynecology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Maha
authors: M
authors: Tulbah
authors: Obstetrics and Gynecology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Maha
authors: M
authors: Alnemer
authors: Obstetrics and Gynecology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Rubina
authors: R
authors: Khan
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Haya
authors: H
authors: Al-Jurayb
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Ahmed
authors: A
authors: Alahmed
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Asma I
authors: AI
authors: Tahir
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Dania
authors: D
authors: Khalil
authors: Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK.
authors: Noel
authors: N
authors: Edwards
authors: Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
authors: Basma
authors: B
authors: Al Abdulaziz
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Faisal S
authors: FS
authors: Binhumaid
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Salma
authors: S
authors: Majid
authors: Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
authors: Tariq
authors: T
authors: Faquih
authors: Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
authors: Mohamed
authors: M
authors: El-Kalioby
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
authors: Mohamed
authors: M
authors: Abouelhoda
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
authors: Nada
authors: N
authors: Altassan
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
authors: Dorota
authors: D
authors: Monies
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
authors: Brian
authors: B
authors: Meyer
authors: Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK.
authors: John A
authors: JA
authors: Sayer
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Mamdouh
authors: M
authors: Albaqumi
mesh_terms: D018912:Arabs / Q000235:genetics; D000072661:Ciliopathies / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D052177:Kidney Diseases, Cystic / Q000151:congenital / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D000072379:NIMA-Related Kinases / Q000235:genetics; D066087:Perinatal Death; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D012529:Saudi Arabia; D013577:Syndrome
chemical_list: C528701:CC2D2A protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; C458529:NEK8 protein, human; D000072379:NIMA-Related Kinases