Title
Medium-chain acyl-coA dehydrogenase (MCAD) deficiency : the prevalent mutation G985 (K304E) is subject to a strong founder effect from Northwestern Europe Medium-chain acyl-coA dehydrogenase (MCAD) deficiency : the prevalent mutation G985 (K304E) is subject to a strong founder effect from Northwestern Europe
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Basel ,
Subject
Human medicine
Source (journal)
Human heredity. - Basel
Volume/pages
43(1993) :6 , p. 342-350
ISSN
0001-5652
ISI
A1993MM85800003
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Medium-chain acyl CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited defect of fatty acid P-oxidation. Approximately 90% of the disease-causing alleles in diagnosed patients are due to a single base mutation, an A (adenine) to G (guanine) transition at position 985 of MCAD cDNA (G985). In a limited number of cases it was found that this mutation was always associated with a particular haplotype, defined by three intragenic restriction fragment length polymorphisms, indicating a founder effect [Kolvraa et al.; Hum Genet 1991;87:425-429]. In addition, recent studies of American patients and their ancestors suggested the existence of a founder from northern Europe [Yokota et al.; Am J Hum Genet 1991;49:1280-1291]. In the present study we document (1) that the G985 heterozygous frequency in the Caucasian population of North Carolina in the USA is 1/84, which is 5- to 10-fold higher than in non-Caucasian Americans; (2) that there exists a 100% association of the G985 mutation in 17 families with MCAD-deficient patients to a certain haplotype, defined by the restriction endonucleases BanII, PstI and TaqI; (3) that MCAD deficiency due to the G985 mutation is more frequent in the Netherlands, Ireland, England, Belgium and Denmark than in other western European countries, and (4) that the frequency distribution of G985 mutation carriers is 1/68-1/101 in newborns in the United Kingdom and Denmark, and 1/333 in Italy, These results support the notion of a founder effect in northwestern Europe.
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