title: Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry.
abstract: Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb upstream of the ADA transcription start site. All patients were homozygous for the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both 0.012 (carrier frequency 2.4%). Based on the analysis of AluVpA alleles, the ADA c7C/T mutation was estimated to be approximately 7,100 years old. Approximately 1 out of 5 - 10000 Somali children will be born with ADA deficiency due to an ADA c7C/T mutation, although within certain clans the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation.
authors.affiliation: Department of Forensic Genetics, Institute of Forensic Medicine, University of Copenhagen, DK-2100 Copenhagen, Denmark. jj.sanchez@mju.es
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Gemma
authors.initials: G
authors.lastname: Monaghan
authors.forename: Claus
authors.initials: C
authors.lastname: Børsting
authors.forename: Gail
authors.initials: G
authors.lastname: Norbury
authors.forename: Niels
authors.initials: N
authors.lastname: Morling
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000483:Alleles; D020087:Alu Elements; D001483:Base Sequence; D018389:Codon, Nonsense; D017931:DNA Primers / Q000235:genetics; D003718:Denmark; D019143:Evolution, Molecular; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008131:London; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D020125:Mutation, Missense; D016511:Severe Combined Immunodeficiency / Q000201:enzymology* / Q000235:genetics*; D012998:Somalia / Q000208:ethnology
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; D000243:Adenosine Deaminase