PMID- 10575540
OWN - NLM
STAT- MEDLINE
DCOM- 19991229
LR  - 20191103
IS  - 1079-9796 (Print)
IS  - 1079-9796 (Linking)
VI  - 25
IP  - 3-4
DP  - 1999 Jun-Aug
TI  - Two novel missense mutations of the HFE gene (I105T and G93R) and identification 
      of the S65C mutation in Alabama hemochromatosis probands.
PG  - 147-55
AB  - 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.
FAU - Barton, J C
AU  - Barton JC
AD  - Southern Iron Disorders Center, Birmingham, Alabama 35209, USA.
      ironmd@dnamail.com
FAU - Sawada-Hirai, R
AU  - Sawada-Hirai R
FAU - Rothenberg, B E
AU  - Rothenberg BE
FAU - Acton, R T
AU  - Acton RT
LA  - eng
GR  - DK32767/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood Cells Mol Dis
JT  - Blood cells, molecules & diseases
JID - 9509932
RN  - 0 (HFE protein, human)
RN  - 0 (HLA Antigens)
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Adult
MH  - Alabama/epidemiology
MH  - Alleles
MH  - Exons/genetics
MH  - Family Health
MH  - Female
MH  - Gene Frequency
MH  - Genes, MHC Class I/*genetics
MH  - Genotype
MH  - HLA Antigens/*genetics/immunology
MH  - Hemochromatosis/epidemiology/*genetics
MH  - Hemochromatosis Protein
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Humans
MH  - Immunophenotyping
MH  - Introns/genetics
MH  - Male
MH  - *Membrane Proteins
MH  - Middle Aged
MH  - Mutation, Missense
MH  - Pedigree
MH  - Point Mutation
MH  - Sequence Analysis, DNA
EDAT- 1999/11/27 00:00
MHDA- 1999/11/27 00:01
CRDT- 1999/11/27 00:00
PHST- 1999/11/27 00:00 [pubmed]
PHST- 1999/11/27 00:01 [medline]
PHST- 1999/11/27 00:00 [entrez]
AID - S1079979699902401 [pii]
AID - 10.1006/bcmd.1999.0240 [doi]
PST - ppublish
SO  - Blood Cells Mol Dis. 1999 Jun-Aug;25(3-4):147-55. doi: 10.1006/bcmd.1999.0240.