DNA sequence abnormalities of human glucose-6-phosphate dehydrogenase variants

Over 400 supposedly biochemically and genetically distinct variants of glucose-6-phosphate dehydrogenase (G6PD) have been described in the past. In order to investigate these variants at the DNA sequence level we have now determined the relevant sequences of introns of G6PD and describe a method whi...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 266; no. 7; pp. 4145 - 4150
Main Authors:	BEUTLER, E, KUHL, W, GELABART, T, FORMAN, L
Format:	Journal Article
Language:	English
Published:	Bethesda, MD American Society for Biochemistry and Molecular Biology 05-03-1991
Subjects:	Analytical, structural and metabolic biochemistry Anemia, Hemolytic, Congenital Nonspherocytic - enzymology Anemia, Hemolytic, Congenital Nonspherocytic - genetics Base Sequence Biological and medical sciences Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Genes Glucosephosphate Dehydrogenase - chemistry Glucosephosphate Dehydrogenase - genetics Glucosephosphate Dehydrogenase - metabolism Humans Introns Molecular Sequence Data Mutation Oligonucleotides - chemistry Oxidoreductases Polymerase Chain Reaction Human Gene Nucleotide sequence Enzyme Glucose-6-phosphate dehydrogenase Binding site Mutation Localization
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Summary:	Over 400 supposedly biochemically and genetically distinct variants of glucose-6-phosphate dehydrogenase (G6PD) have been described in the past. In order to investigate these variants at the DNA sequence level we have now determined the relevant sequences of introns of G6PD and describe a method which allows us to rapidly determine the sequence of the entire coding region of G6PD. This technique was applied to six variants that cause G6PD deficiency to be functionally so severe as to result in nonspherocytic hemolytic anemia. Although the patients were all unrelated, G6PD Marion, Gastonia, and Minnesota each had identical mutations, a G---T at nucleotide (nt) 637 in exon 6 leading to a Val---Leu substitution at amino acid 213. The mutations of Nashville and Anaheim were identical to each other, viz. G---A at nt 1178 in exon 10 producing a Arg---His substitution at amino acid 393. G6PD Loma Linda had a C---A substitution at nt 1089 in exon 10, producing a Asn---Lys change at amino acid 363. The results confirm our earlier results suggesting that the NADP-binding site is in a small region of exon 10 and suggest the possibility that this area is also concerned with the binding of glucose-6-P.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0021-9258 1083-351X
DOI:	10.1016/S0021-9258(20)64298-3