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Molecular characterization of Duarte-1 and Duarte-2 variants of galactose-1-phosphate uridyltransferase.
J Inherit Metab Dis. 1996; 19(5):638-44.JI

Abstract

The N314D polymorphism was found in two different alleles of the galactose-1-phosphate uridyltransferase (GALT) gene, Duarte-1 (D1) and Duarte-2 (D2). Although both variants have identical electrophoretic mobility and isoelectro-focusing points, the galactose-1-phosphate uridyltransferase (GALT) activity varies: D1 alleles showed 110-130% of the normal RBC activity, but D2 alleles only 40-50%. We found that D1 alleles also carried a silent mutation in exon 7 (L218L) in addition to N314D. In contrast, besides N314D, D2 alleles carried two regulatory mutations, G1105C and G1391A, in introns D and E, respectively. In normal and Q188R alleles none of the above four mutations coexisted. However, some galactosaemia alleles with mutations other than Q188R, such as W316X and E340X of exon 10, also carried the N314D mutation. The W316X alleles existed in cis with the intron mutations (G1105C and G1391A), whereas those with E340X are in cis with L218L. In all cases examined, the intron mutations were not found in D1 alleles and no D2 alleles had the silent mutation of L218L. These results suggest that the decrease in the GALT activity in D2 may be due to regulation of the GALT gene expression. The G1105C site may be critical to the function of erythroid transcription factor NF-E1, since it flanks the core consensus sequence for one of its binding sites. The G1391A mutation may affect another cis-acting regulatory sequence. Alternatively, both mutations may be involved in an aberrant splice processing, which possibly results in a low level of correctly spliced mRNA.

Authors+Show Affiliations

Medizinisch Immunologische Laboratorien, München, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8892021

Citation

Podskarbi, T, et al. "Molecular Characterization of Duarte-1 and Duarte-2 Variants of Galactose-1-phosphate Uridyltransferase." Journal of Inherited Metabolic Disease, vol. 19, no. 5, 1996, pp. 638-44.
Podskarbi T, Kohlmetz T, Gathof BS, et al. Molecular characterization of Duarte-1 and Duarte-2 variants of galactose-1-phosphate uridyltransferase. J Inherit Metab Dis. 1996;19(5):638-44.
Podskarbi, T., Kohlmetz, T., Gathof, B. S., Kleinlein, B., Bieger, W. P., Gresser, U., & Shin, Y. S. (1996). Molecular characterization of Duarte-1 and Duarte-2 variants of galactose-1-phosphate uridyltransferase. Journal of Inherited Metabolic Disease, 19(5), 638-44.
Podskarbi T, et al. Molecular Characterization of Duarte-1 and Duarte-2 Variants of Galactose-1-phosphate Uridyltransferase. J Inherit Metab Dis. 1996;19(5):638-44. PubMed PMID: 8892021.
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TY - JOUR T1 - Molecular characterization of Duarte-1 and Duarte-2 variants of galactose-1-phosphate uridyltransferase. AU - Podskarbi,T, AU - Kohlmetz,T, AU - Gathof,B S, AU - Kleinlein,B, AU - Bieger,W P, AU - Gresser,U, AU - Shin,Y S, PY - 1996/1/1/pubmed PY - 1996/1/1/medline PY - 1996/1/1/entrez SP - 638 EP - 44 JF - Journal of inherited metabolic disease JO - J Inherit Metab Dis VL - 19 IS - 5 N2 - The N314D polymorphism was found in two different alleles of the galactose-1-phosphate uridyltransferase (GALT) gene, Duarte-1 (D1) and Duarte-2 (D2). Although both variants have identical electrophoretic mobility and isoelectro-focusing points, the galactose-1-phosphate uridyltransferase (GALT) activity varies: D1 alleles showed 110-130% of the normal RBC activity, but D2 alleles only 40-50%. We found that D1 alleles also carried a silent mutation in exon 7 (L218L) in addition to N314D. In contrast, besides N314D, D2 alleles carried two regulatory mutations, G1105C and G1391A, in introns D and E, respectively. In normal and Q188R alleles none of the above four mutations coexisted. However, some galactosaemia alleles with mutations other than Q188R, such as W316X and E340X of exon 10, also carried the N314D mutation. The W316X alleles existed in cis with the intron mutations (G1105C and G1391A), whereas those with E340X are in cis with L218L. In all cases examined, the intron mutations were not found in D1 alleles and no D2 alleles had the silent mutation of L218L. These results suggest that the decrease in the GALT activity in D2 may be due to regulation of the GALT gene expression. The G1105C site may be critical to the function of erythroid transcription factor NF-E1, since it flanks the core consensus sequence for one of its binding sites. The G1391A mutation may affect another cis-acting regulatory sequence. Alternatively, both mutations may be involved in an aberrant splice processing, which possibly results in a low level of correctly spliced mRNA. SN - 0141-8955 UR - https://www.unboundmedicine.com/medline/citation/8892021/Molecular_characterization_of_Duarte_1_and_Duarte_2_variants_of_galactose_1_phosphate_uridyltransferase_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0141-8955&date=1996&volume=19&issue=5&spage=638 DB - PRIME DP - Unbound Medicine ER -