Conference Proceedings

Exome Sequencing Identifies a GNPAT Variant Associated with Severe Iron Overload in HFE C282Y Homozygous Men with Extreme Phenotypes; Possible Role in Regulation of Hepcidin Expression

Gordon D McLaren, Mary J Emond, V Nathan Subramaniam, Pradyumna D Phatak, James C Barton, Paul C Adams, Justin B Goh, Cameron J McDonald, Lawrie W Powell, Lyle C Gurrin, Katrina J Allen, Deborah A Nickerson, Tin Louie, Grant A Ramm, Gregory J Anderson, Christine E McLaren

BLOOD | AMER SOC HEMATOLOGY | Published : 2014


Abstract Variability in the severity of iron overload among homozygotes for the HFE C282Y polymorphism is one of the major unsolved problems in our understanding of hereditary hemochromatosis (HH). We previously conducted exome sequencing of DNA from 35 HFE C282Y male homozygotes with either markedly increased iron stores (n=22; cases) or normal to mildly increased iron stores (n=13; controls) to identify rare and common causal variants associated with variability of disease expression in HH. The 35 participants, residents of the U.S., Canada, and Australia, reported little or no alcohol consumption. Criteria for HFE C282Y homozygotes with increased iron stores..

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