title: A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families.
abstract: Nephrotic syndrome (NS) is a renal disease characterized by heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia. Its presentation within the first 3 months of life or in multiple family members suggests an underlying inherited cause. To determine the frequency of inherited NS, 62 cases (representing 49 families with NS) from Saudi Arabia were screened for mutations in NPHS1, NPHS2, LAMB2, PLCE1, CD2AP, MYO1E, WT1, PTPRO and Nei endonuclease VIII-like 1 (NEIL1). We detected likely causative mutations in 25 out of 49 families studied (51%). We found that the most common genetic cause of NS in our cohort was a homozygous mutation in the NPHS2 gene, found in 11 of the 49 families (22%). Mutations in the NPHS1 and PLCE1 genes allowed a molecular genetic diagnosis in 12% and 8% of families, respectively. We detected novel MYO1E mutations in three families (6%). No mutations were found in WT1, PTPRO or NEIL1. The pathogenicity of novel variants was analyzed by in silico tests and by genetic screening of ethnically matched control populations. This is the first report describing the molecular genetics of NS in the Arabian Peninsula.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Al-Hamed
authors.forename: Essam
authors.initials: E
authors.lastname: Al-Sabban
authors.forename: Hamad
authors.initials: H
authors.lastname: Al-Mojalli
authors.forename: Naffaa
authors.initials: N
authors.lastname: Al-Harbi
authors.forename: Eissa
authors.initials: E
authors.lastname: Faqeih
authors.forename: Hammad
authors.initials: H
authors.lastname: Al Shaya
authors.forename: Khalid
authors.initials: K
authors.lastname: Alhasan
authors.forename: Safaa
authors.initials: S
authors.lastname: Al-Hissi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rajab
authors.forename: Noel
authors.initials: N
authors.lastname: Edwards
authors.forename: Abbas
authors.initials: A
authors.lastname: Al-Abbad
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Hassoun
authors.forename: John A
authors.initials: JA
authors.lastname: Sayer
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D024461:Myosin Type I / Q000235:genetics; D009404:Nephrotic Syndrome / Q000235:genetics*; D054801:Phosphoinositide Phospholipase C / Q000235:genetics; D012529:Saudi Arabia
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon; C511011:MYO1E protein, human; D024461:Myosin Type I