The most common mutation causing medium-chain acyl-CoA dehydrogenase deficiency is strongly associated with a particular haplotype in the region of the gene

• Published in: Human genetics 1991-08, Vol.87 (4), p.425-428
• Main Authors: KOLVRAA, S, GREGERSEN, N, BOLUND, L, BLAKEMORE, A. I. F, SCHNEIDERMANN, A. K, WINTER, V, ANDRESEN, B. S, CURTIS, D, ENGEL, P. C, PRICILLE, D, RHEAD, W
• Format: Article
• Language: English
• Subjects: Acyl-CoA Dehydrogenase; Acyl-CoA Dehydrogenases - deficiency; Acyl-CoA Dehydrogenases - genetics; Biological and medical sciences; DNA - genetics; Errors of metabolism; genes; Haplotypes; Heterozygote; Homozygote; Humans; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mutation; point mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; restriction fragment length polymorphism
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/BF00197161

RFLP haplotypes in the region containing the medium-chain acyl-CoA dehydrogenase (MCAD) gene on chromosome 1 have been determined in patients with MCAD deficiency. The RFLPs were detected after digestion of patient DNA with the enzymes BanII. PstI and TaqI and with an MCAD cDNA-clone as a probe. Of 32 disease-causing alleles studied, 31 possessed the previously published A---G point-mutation at position 985 of the cDNA. This mutation has been shown to result in inactivity of the MCAD enzyme. In at least 30 of the 31 alleles carrying this G985 mutation a specific RFLP haplotype was present. In contrast, the same haplotype was present in only 23% of normal alleles (P less than or equal to 3.4 x 10(-18)). These findings are consistent with the existence of a pronounced founder effect, possibly combined with biological and/or sampling selection.