title: [Mutation analysis of the pathogenic gene in a Chinese family with hereditary hemochromatosis].
abstract: Hereditary hemochromatosis (HHC) is a rare autosomal recessive disorder. We recruited a consanguineous Chinese family including the proband with HHC and other four members without HHC. Using whole-exome sequencing, we identified two homozygous mutations (c.G18C [p.Q6H] and c.GC962_963AA [p.C321X]) in the hemojuvelin gene (HJV) in the proband with HHC. No mutation was found in other four previously identified HHC related genes, HAMP, TFR2, FPN and HFE. The functional impact of p.Q6H mutation is weak whereas p.C321X, a premature termination mutation, results in a truncated HJV protein, which lacks the glycosylphosphatidylinositol (GPI) anchor domain. In addition to the mutations in HJV, other 12 homozygous mutations were identified in this patient. However, none of these mutations showed strong damaging impact and the mutated genes are not related to iron metabolism. Our in-house data further demonstrated that p.C321X is absent in the general Chinese population, suggesting that the homozygous mutation p.C321X in HJV is causative in the patient with HHC. Accordingly, all of the four members without HHC from the same family carried wild-type alleles or heterozygous mutations, but not the homozygous mutation in this site. Thus, we found for the first time that the homozygous mutation p.C321X in HJV can result in HHC, which will help genetic diagnosis and prenatal counseling for HHC.
authors.affiliation: 1. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; 2. National Engineering Research Center for Protein Drugs, Beijing 102206, China; 3. National Center for Protein Sciences in Beijing, Beijing 102206, China;
authors.forename: Li
authors.initials: L
authors.lastname: Yuanfeng
authors.affiliation: 1. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; 2. National Engineering Research Center for Protein Drugs, Beijing 102206, China; 3. National Center for Protein Sciences in Beijing, Beijing 102206, China;
authors.forename: Zhang
authors.initials: Z
authors.lastname: Hongxing
authors.affiliation: 1. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; 2. National Engineering Research Center for Protein Drugs, Beijing 102206, China; 3. National Center for Protein Sciences in Beijing, Beijing 102206, China;
authors.forename: Zhang
authors.initials: Z
authors.lastname: Haitao
authors.affiliation: Poisoning Treatment Department, No.307 Hospital of People.
authors.forename: Peng
authors.initials: P
authors.lastname: Xiaobo
authors.affiliation: Poisoning Treatment Department, No.307 Hospital of People.
authors.forename: Bai
authors.initials: B
authors.lastname: Lili
authors.affiliation: 1. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; 2. National Engineering Research Center for Protein Drugs, Beijing 102206, China; 3. National Center for Protein Sciences in Beijing, Beijing 102206, China;
authors.forename: He
authors.initials: H
authors.lastname: Fuchu
authors.affiliation: Poisoning Treatment Department, No.307 Hospital of People.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zewu
authors.affiliation: 1. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; 2. National Engineering Research Center for Protein Drugs, Beijing 102206, China; 3. National Center for Protein Sciences in Beijing, Beijing 102206, China;
authors.forename: Zhou
authors.initials: Z
authors.lastname: Gangqiao
mesh_terms: D000328:Adult; D059472:Exome; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins