Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Annals of Human Genetics |
| Vol/bind | 71 |
| Udgave nummer | Pt 3 |
| Sider (fra-til) | 336-47 |
| Antal sider | 11 |
| ISSN | 0003-4800 |
| DOI | |
| Status | Udgivet - 2007 |
Bibliografisk note
Keywords: Adenosine Deaminase; Alleles; Alu Elements; Base Sequence; Codon, Nonsense; DNA Primers; Denmark; Evolution, Molecular; Female; Founder Effect; Gene Frequency; Haplotypes; Heterozygote; Humans; Infant; Infant, Newborn; London; Male; Microsatellite Repeats; Models, Genetic; Mutation, Missense; Severe Combined Immunodeficiency; SomaliaAdgang til dokumentet
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I: Annals of Human Genetics, Bind 71, Nr. Pt 3, 2007, s. 336-47.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - 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
AU - Sanchez Sanchez, Juan Jose
AU - Monaghan, Gemma
AU - Børsting, Claus
AU - Norbury, Gail
AU - Morling, Niels
AU - Gaspar, H Bobby
N1 - Keywords: Adenosine Deaminase; Alleles; Alu Elements; Base Sequence; Codon, Nonsense; DNA Primers; Denmark; Evolution, Molecular; Female; Founder Effect; Gene Frequency; Haplotypes; Heterozygote; Humans; Infant; Infant, Newborn; London; Male; Microsatellite Repeats; Models, Genetic; Mutation, Missense; Severe Combined Immunodeficiency; Somalia
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1111/j.1469-1809.2006.00338.x
DO - 10.1111/j.1469-1809.2006.00338.x
M3 - Journal article
C2 - 17181544
SN - 0003-4800
VL - 71
SP - 336
EP - 347
JO - Annals of Human Genetics
JF - Annals of Human Genetics
IS - Pt 3
ER -