A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote

Wallace D.F., Dooley J.S. and Walker A.P. (1999) A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote. Gastroenterology, 116 6: 1409-1412. doi:10.1016/S0016-5085(99)70505-6


Author Wallace D.F.
Dooley J.S.
Walker A.P.
Title A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote
Journal name Gastroenterology   Check publisher's open access policy
ISSN 0016-5085
Publication date 1999-01-01
Year available 1999
Sub-type Article (original research)
DOI 10.1016/S0016-5085(99)70505-6
Open Access Status
Volume 116
Issue 6
Start page 1409
End page 1412
Total pages 4
Place of publication PHILADELPHIA
Publisher W B SAUNDERS CO-ELSEVIER INC
Language eng
Subject 2715 Gastroenterology
Abstract Background & Aims: Most patients with genetic hemochromatosis are homozygous for a single mutation of the HFE gene (C282Y). There is a second mutation, H63D, but its role in iron overload is less conclusive. The aim of this study was to investigate the basis of iron overload in a patient with classical hemochromatosis who was only heterozygous for C282Y and negative for H63D. Methods: Genotype for the C282Y, H63D, and S65C mutations of HFE was determined in patient RFH, his family members, and 365 controls. The HFE gene was sequenced in patient RFH. Allele-specific reverse-transcription polymerase chain reaction was performed to investigate RNA splicing. Allele frequency was determined by allele-specific oligonucleotide hybridization. Results: The patient is compound heterozygous for C282Y and a novel splice site mutation (IVS3 + 1G --> T). His sister has an identical genotype and elevated serum ferritin and transferrin saturation. The novel mutation functionally alters messenger RNA splicing, causing obligate skipping of exon 3. However, the IVS3 + 1G --> T mutation was found to be rare and was not detected in 630 control European chromosomes. Conclusions: IVS3 + 1G --> T in the compound heterozygous state with C282Y results in iron overload that can progress to a severe phenotype of classical hemochromatosis. The demonstration of IVS3 + 1G --> T highlights the possibility of other rare HFE mutations, particularly in C282Y heterozygotes with iron overload.
Keyword Gastroenterology & Hepatology
Gastroenterology & Hepatology
GASTROENTEROLOGY & HEPATOLOGY
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
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