A common mutation associated with the Duarte galactosemia allele

Journal Article · Wed Jun 01 00:00:00 EDT 1994 · American Journal of Human Genetics; (United States)

OSTI ID:7076115

Elsas, L J; Dembure, P P; Langley, S; Paulk, E M; Hjelm, L N; Fridovich-Keil, J ^[1]

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1. Emory Univ. School of Medicine, Atlanta, GA (United States)

The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalant mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have [approximately]75%, 50%, and 25% of normal GALT activity, respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here the authors systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, a transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. The authors conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. 36 refs., 3 figs., 2 tabs.

• OSTI ID: 7076115
• Journal Information: American Journal of Human Genetics; (United States), Vol. 54:6; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GALACTOSE
METABOLIC DISEASES
GLYCOSYL TRANSFERASES
GENE MUTATIONS
DNA SEQUENCING
DNA-CLONING
UDPG
ALDEHYDES
CARBOHYDRATES
CLONING
DISEASES
DNA HYBRIDIZATION
ENZYMES
GLYCOSIDES
HEXOSES
HYBRIDIZATION
MONOSACCHARIDES
MUTATIONS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PROTEINS
SACCHARIDES
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
550400* - Genetics
550900 - Pathology