A common mutation in the CBS gene explains a high incidence of homocystinuria in the Qatari population.
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.
El-Said
Mahmoud F
MF
Pediatric Neurology Unit, Hamad Medical Corporation, Doha, Qatar.
Badii
Ramin
R
Bessisso
M S
MS
Shahbek
Noora
N
El-Ali
Mariam G
MG
El-Marikhie
Mariam
M
El-Zyoid
M
M
Salem
M S Z
MS
Bener
Abdulbari
A
Hoffmann
Georg F
GF
Zschocke
Johannes
J
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
D003541:Cystathionine beta-Synthase