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
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.
Document Type: Research Article
Affiliations: 1: Department of Forensic Genetics, Institute of Forensic Medicine, University of Copenhagen, DK-2100 Copenhagen, Denmark 2: Regional Molecular Genetics, Great Ormond Street Hospital NHS Trust, Great Ormond Street, London WC1N 3JH, United Kingdom 3: Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street London WC1N 1EH, United Kingdom
Publication date: May 1, 2007