Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs

• Published in: Clinical genetics 2011-01, Vol.79 (1), p.60-70
• Main Authors: Shaheen, R, Al-Dirbashi, OY, Al-Hassnan, ZN, Al-Owain, M, Makhsheed, N, Basheeri, F, Seidahmed, MZ, Salih, MAM, Faqih, E, Zaidan, H, Al-Sayed, M, Rahbeeni, Z, Al-Sheddi, T, Hashem, M, Kurdi, W, Shimozawa, N, Alkuraya, FS
• Format: Article
• Language: English
• Subjects: Arab people; Arabs; bifunctional; Biochemistry; Biological and medical sciences; Child, Preschool; Classical genetics, quantitative genetics, hybrids; Clinical medicine; Cytogenetic Analysis; Disease; Female; founder mutation; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic Association Studies; Genetic Heterogeneity; Genetics of eukaryotes. Biological and molecular evolution; homozygosity mapping; Human; Humans; Indexing in process; Infant; Infant, Newborn; Male; Medical genetics; Medical sciences; Middle East; Molecular and cellular biology; Molecular biology; Mutation; peroxisomal; Peroxisomal Disorders - ethnology; Peroxisomal Disorders - genetics; Peroxisomal Disorders - metabolism; Peroxisomal Disorders - physiopathology; Peroxisomes - genetics; Peroxisomes - metabolism; Population genetics, reproduction patterns; Sequence Analysis; splice site mutation; very long-chain fatty acid
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01498.x

Shaheen R, Al‐Dirbashi OY, Al‐Hassnan ZN, Al‐Owain M, Makhsheed N, Basheeri F, Seidahmed MZ, Salih MAM, Faqih E, Zaidan H, Al‐Sayed M, Rahbeeni Z, Al‐Sheddi T, Hashem M, Kurdi W, Shimozawa N, Alkuraya FS. Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs. 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.