BACKGROUND/AIMS: HFE-related haemochromatosis is a common disorder of iron metabolism. Most affected individuals are homozygous for the C282Y mutation of HFE. Some are compound heterozygotes for C282Y/H63D. A small proportion have neither of these genotypes. We have investigated the phenotype of compound heterozygotes for C282Y and another missense mutation S65C. METHODS: Genotype for the S65C mutation was determined in 309 subjects heterozygous for C282Y and negative for H63D, referred because of increased serum iron indices or family screening. A control sample comprising 315 individuals was also studied. RESULTS: Twelve individuals were compound heterozygotes for C282Y and S65C. Seven, referred for family screening, had normal serum iron indices. Five subjects had elevated serum iron indices; three of these had elevated hepatic iron and have received treatment for iron overload. Transferrin saturation was significantly elevated in C282Y/S65C compound heterozygotes compared with simple C282Y heterozygotes. CONCLUSIONS: Some C282Y/S65C compound heterozygotes have elevated serum iron indices and iron overload. The penetrance of this genotype is low and other genetic and environmental factors may influence the expression of iron loading. Screening for S65C may be useful in individuals with iron overload who are not homozygous for C282Y or compound heterozygous for C282Y/H63D.
BACKGROUND/AIMS: HFE-related haemochromatosis is a common disorder of iron metabolism. Most affected individuals are homozygous for the C282Y mutation of HFE. Some are compound heterozygotes for C282Y/H63D. A small proportion have neither of these genotypes. We have investigated the phenotype of compound heterozygotes for C282Y and another missense mutation S65C. METHODS: Genotype for the S65C mutation was determined in 309 subjects heterozygous for C282Y and negative for H63D, referred because of increased serum iron indices or family screening. A control sample comprising 315 individuals was also studied. RESULTS: Twelve individuals were compound heterozygotes for C282Y and S65C. Seven, referred for family screening, had normal serum iron indices. Five subjects had elevated serum iron indices; three of these had elevated hepatic iron and have received treatment for iron overload. Transferrin saturation was significantly elevated in C282Y/S65C compound heterozygotes compared with simple C282Y heterozygotes. CONCLUSIONS: Some C282Y/S65C compound heterozygotes have elevated serum iron indices and iron overload. The penetrance of this genotype is low and other genetic and environmental factors may influence the expression of iron loading. Screening for S65C may be useful in individuals with iron overload who are not homozygous for C282Y or compound heterozygous for C282Y/H63D.
Authors: Gioconda Dias Rodrigues Leão; Juliana Mendonça Freire; Andrea Luciana Araújo Cunha Fernandes; Taissa Maria Moura de Oliveira; Nilma Dias Leão; Erica Aires Gil; Roberto Chaves de Vasconcelos; João Paulo da Silva Azevedo; Valéria Soraya de Farias Sales; Telma Maria de Araújo Moura Lemos; Marcos Dias Leão; Francisco Fernandes do Nascimento; James Farley Rafael Maciel; Rodrigo Villar de Freitas; Aldair de Souza Paiva; Geraldo Barroso Cavalcanti Journal: J Clin Lab Anal Date: 2014-01-06 Impact factor: 2.352
Authors: Claudia C Branco; Cidália T Gomes; Laura De Fez; Sara Bulhões; Maria José Brilhante; Tânia Pereirinha; Rita Cabral; Ana Catarina Rego; Cristina Fraga; António G Miguel; Gracinda Brasil; Paula Macedo; Luisa Mota-Vieira Journal: PLoS One Date: 2015-10-26 Impact factor: 3.240