title: Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs.
abstract: Peroxisomes are single membrane-bound cellular organelles that carry out critical metabolic reactions perturbation of which leads to an array of clinical phenotypes known as peroxisomal disorders (PD). In this study, the largest of its kind in the Middle East, we sought to comprehensively characterize these rare disorders at the clinical, biochemical and molecular levels. Over a 2-year period, we have enrolled 17 patients representing 16 Arab families. Zellweger-spectrum phenotype was observed in 12 patients and the remaining 5 had the rhizomelic chondrodysplasia punctata phenotype. We show that homozygosity mapping is a cost-effective strategy that enabled the identification of the underlying genetic defect in 100% of the cases. The pathogenic nature of the mutations identified was confirmed by immunofluorescence and complementation assays. We confirm the genetic heterogeneity of PD in our population, expand the pool of pathogenic alleles and draw some phenotype/genotype correlations.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: R
authors.initials: R
authors.lastname: Shaheen
authors.forename: O Y
authors.initials: OY
authors.lastname: Al-Dirbashi
authors.forename: Z N
authors.initials: ZN
authors.lastname: Al-Hassnan
authors.forename: M
authors.initials: M
authors.lastname: Al-Owain
authors.forename: N
authors.initials: N
authors.lastname: Makhsheed
authors.forename: F
authors.initials: F
authors.lastname: Basheeri
authors.forename: M Z
authors.initials: MZ
authors.lastname: Seidahmed
authors.forename: M A M
authors.initials: MA
authors.lastname: Salih
authors.forename: E
authors.initials: E
authors.lastname: Faqih
authors.forename: H
authors.initials: H
authors.lastname: Zaidan
authors.forename: M
authors.initials: M
authors.lastname: Al-Sayed
authors.forename: Z
authors.initials: Z
authors.lastname: Rahbeeni
authors.forename: T
authors.initials: T
authors.lastname: Al-Sheddi
authors.forename: M
authors.initials: M
authors.lastname: Hashem
authors.forename: W
authors.initials: W
authors.lastname: Kurdi
authors.forename: N
authors.initials: N
authors.lastname: Shimozawa
authors.forename: F S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D018912:Arabs; D002675:Child, Preschool; D020732:Cytogenetic Analysis; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008877:Middle East; D009154:Mutation; D018901:Peroxisomal Disorders / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020675:Peroxisomes / Q000235:genetics* / Q000378:metabolism; D017421:Sequence Analysis