title: Case Report: Whole-exome analysis of a child with polycystic kidney disease and ventriculomegaly.
abstract: Autosomal recessive polycystic kidney disease (ARPKD) is an inherited ciliopathy leading to progressive kidney and liver disease. Biallelic mutations in the PKHD1 gene underlie this condition. We describe a child with bilaterally enlarged cystic kidneys, portal hypertension, and cerebral ventriculomegaly. Molecular genetic investigations using whole-exome sequencing and confirmation using Sanger sequencing revealed a homozygous pathogenic mutation in PKHD1 underlying the clinical phenotype of ARPKD. Whole-exome data analysis was used to search for additional rare variants in additional ciliopathy genes that may have contributed to the unusual brain phenotype. Aside from a rare hypomorphic allele in MKS1, no other pathogenic variants were detected. We conclude that the homozygous pathogenic mutation in PKHD1 underlies the ciliopathy phenotype in this patient.
authors.affiliation: Department of Pediatrics, Kasr Al Ainy School of Medicine, Center of Pediatric Nephrology and Transplantation, Cairo University, Egyptian Group for Orphan Renal Diseases, Cairo, Egypt.
authors.forename: M M
authors.initials: MM
authors.lastname: Nabhan
authors.affiliation: Department of Pediatrics, Kasr Al Ainy School of Medicine, Center of Pediatric Nephrology and Transplantation, Cairo University, Egyptian Group for Orphan Renal Diseases, Cairo, Egypt.
authors.forename: H
authors.initials: H
authors.lastname: Abdelaziz
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle-Upon-Tyne, United Kingdom.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Clinical and Chemical Pathology, Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: R
authors.initials: R
authors.lastname: El Sayed
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle-Upon-Tyne, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Santibanez-Koref
authors.affiliation: Department of Pediatrics, Kasr Al Ainy School of Medicine, Center of Pediatric Nephrology and Transplantation, Cairo University, Egyptian Group for Orphan Renal Diseases, Cairo, Egypt.
authors.forename: N A
authors.initials: NA
authors.lastname: Soliman
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle-Upon-Tyne, United Kingdom john.sayer@ncl.ac.uk.
authors.forename: J A
authors.initials: JA
authors.lastname: Sayer
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D059472:Exome / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface