title: A common mutation in the CBS gene explains a high incidence of homocystinuria in the Qatari population.
abstract: We report the results of a study carried out to delineate genetic and epidemiological aspects of homocystinuria in the Qatari population. Sixty-four patients with homocystinuria (37 males, 27 females, age 1 to 29 years) from 31 nuclear families were ascertained over a period of more than four years. The incidence of homocystinuria in Qatar was calculated to be > or =1:3000, the highest in the world known so far. All patients in whom data were available were vitamin B6-nonresponsive. Molecular studies were performed in all patients. All 53 patients from tribe M and all three patients from tribe K were homozygous for the mutation c.1006C>T (p.R336C) in the CBS gene, with an additional seven patients resulting from mixed marriages between tribe M and tribe K. A single patient from tribe S was homozygous for mutation c.700G>A (p.D234N) in the CBS gene. Both mutations have been previously reported but involve hypermutable CpG dinculeotides and may be recurrent mutations in the Qatari population. The results of this study illustrate a strong founder effect causing a high prevalence of an autosomal recessive disease in a highly consanguineous Arabian population. Molecular neonatal screening may be suitable for early detection of homocystinuria in this population.
authors.affiliation: Pediatric Neurology Unit, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Mahmoud F
authors.initials: MF
authors.lastname: El-Said
authors.forename: Ramin
authors.initials: R
authors.lastname: Badii
authors.forename: M S
authors.initials: MS
authors.lastname: Bessisso
authors.forename: Noora
authors.initials: N
authors.lastname: Shahbek
authors.forename: Mariam G
authors.initials: MG
authors.lastname: El-Ali
authors.forename: Mariam
authors.initials: M
authors.lastname: El-Marikhie
authors.forename: M
authors.initials: M
authors.lastname: El-Zyoid
authors.forename: M S Z
authors.initials: MS
authors.lastname: Salem
authors.forename: Abdulbari
authors.initials: A
authors.lastname: Bener
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D006712:Homocystinuria / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D011780:Qatar / Q000453:epidemiology
chemical_list: D003541:Cystathionine beta-Synthase