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Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands.
Blood Cells Mol Dis. 1999 Jun-Aug; 25(3-4):147-55.BC

Abstract

Sequencing of HFE exons 2, 3, 4, and 5, and of portions of introns 2, 4, and 5 revealed novel mutations in four of twenty hemochromatosis probands who lacked C282Y homozygosity, C282Y/H63D compound heterozygosity, or H63D homozygosity. Probands 1 and 2 were heterozygous for previously undescribed mutations: exon 2, nt 314T-->C (314C; I105T), and exon 2, nt 277G-->(277C; G93R), respectively; these probands were also heterozygous for H63D and C282Y, respectively. Probands 3 and 4 were heterozygous for a previously described but uncommon HFE mutation: exon 2, nt 193A-->T (193T; S65C). Proband 3 was also heterozygous for C282Y and had porphyria cutanea tarda, and Proband 4 had hereditary stomatocytosis. Each of these four probands had iron overload. In each proband with an uncommon HFE coding region mutation, I105T, G93R, and S65C occurred on separate chromosomes from those with the C282Y or H63D mutations. Neither I105T, G93R, nor S65C occurred as spontaneous mutations in our probands. The I105T and G93R mutations were linked to haplotypes bearing HLA-A3,-B7 and HLA-A2,-B62, respectively. The S65C mutation was linked to a haplotype characterized by HLA-32. Sixteen other probands did not have an uncommon HFE exon mutation. In 176 normal control subjects, two were heterozygous for S65C, but I105T and G93R were not detected. Nine of twenty probands were heterozygous and two probands were homozygous for a previously described base-pair change at intron 2, nt 3671T-->C. One proband without a detectable missense mutation had a previously described intron 5 allele (nt 6700G-->A). Heterozygosity for a previously described base-pair change in intron 4 (nt 5636T-->C) was detected in all persons we studied who also had the S65C mutation. One proband was heterozygous for a previously undescribed base-pair change at intron 5 (nt 5807A-->G). We conclude that uncommon HFE exon and intron mutations may be discovered among hemochromatosis patients who have "atypical" HFE genotypes.

Authors+Show Affiliations

Southern Iron Disorders Center, Birmingham, Alabama 35209, USA. ironmd@dnamail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10575540

Citation

Barton, J C., et al. "Two Novel Missense Mutations of the HFE Gene (I105T and G93R) and Identification of the S65C Mutation in Alabama Hemochromatosis Probands." Blood Cells, Molecules & Diseases, vol. 25, no. 3-4, 1999, pp. 147-55.
Barton JC, Sawada-Hirai R, Rothenberg BE, et al. Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. Blood Cells Mol Dis. 1999;25(3-4):147-55.
Barton, J. C., Sawada-Hirai, R., Rothenberg, B. E., & Acton, R. T. (1999). Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. Blood Cells, Molecules & Diseases, 25(3-4), 147-55.
Barton JC, et al. Two Novel Missense Mutations of the HFE Gene (I105T and G93R) and Identification of the S65C Mutation in Alabama Hemochromatosis Probands. Blood Cells Mol Dis. 1999 Jun-Aug;25(3-4):147-55. PubMed PMID: 10575540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. AU - Barton,J C, AU - Sawada-Hirai,R, AU - Rothenberg,B E, AU - Acton,R T, PY - 1999/11/27/pubmed PY - 1999/11/27/medline PY - 1999/11/27/entrez SP - 147 EP - 55 JF - Blood cells, molecules & diseases JO - Blood Cells Mol Dis VL - 25 IS - 3-4 N2 - Sequencing of HFE exons 2, 3, 4, and 5, and of portions of introns 2, 4, and 5 revealed novel mutations in four of twenty hemochromatosis probands who lacked C282Y homozygosity, C282Y/H63D compound heterozygosity, or H63D homozygosity. Probands 1 and 2 were heterozygous for previously undescribed mutations: exon 2, nt 314T-->C (314C; I105T), and exon 2, nt 277G-->(277C; G93R), respectively; these probands were also heterozygous for H63D and C282Y, respectively. Probands 3 and 4 were heterozygous for a previously described but uncommon HFE mutation: exon 2, nt 193A-->T (193T; S65C). Proband 3 was also heterozygous for C282Y and had porphyria cutanea tarda, and Proband 4 had hereditary stomatocytosis. Each of these four probands had iron overload. In each proband with an uncommon HFE coding region mutation, I105T, G93R, and S65C occurred on separate chromosomes from those with the C282Y or H63D mutations. Neither I105T, G93R, nor S65C occurred as spontaneous mutations in our probands. The I105T and G93R mutations were linked to haplotypes bearing HLA-A3,-B7 and HLA-A2,-B62, respectively. The S65C mutation was linked to a haplotype characterized by HLA-32. Sixteen other probands did not have an uncommon HFE exon mutation. In 176 normal control subjects, two were heterozygous for S65C, but I105T and G93R were not detected. Nine of twenty probands were heterozygous and two probands were homozygous for a previously described base-pair change at intron 2, nt 3671T-->C. One proband without a detectable missense mutation had a previously described intron 5 allele (nt 6700G-->A). Heterozygosity for a previously described base-pair change in intron 4 (nt 5636T-->C) was detected in all persons we studied who also had the S65C mutation. One proband was heterozygous for a previously undescribed base-pair change at intron 5 (nt 5807A-->G). We conclude that uncommon HFE exon and intron mutations may be discovered among hemochromatosis patients who have "atypical" HFE genotypes. SN - 1079-9796 UR - https://www.unboundmedicine.com/medline/citation/10575540/Two_novel_missense_mutations_of_the_HFE_gene__I105T_and_G93R__and_identification_of_the_S65C_mutation_in_Alabama_hemochromatosis_probands_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1079979699902401 DB - PRIME DP - Unbound Medicine ER -