title: A Q312X mutation in the hemojuvelin gene is associated with cardiomyopathy due to juvenile haemochromatosis.
abstract: OBJECTIVE
  Juvenile haemochromatosis (JH) is an autosomal recessive iron disorder characterized by the early onset of secondary cardiomyopathy. The candidate modifier genes are hemojuvelin (HJV) and hepcidin antimicrobial peptide (HAMP). In the Japanese population, the prevalence of JH is quite low. The influence of HJV mutation on the JH phenotype is still unclear.
  
  
  RESULTS
  We searched for possible mutations in a Japanese family with 2 members who were JH patients with severe heart failure. To search for possible variants in the HJV and HAMP genes, we performed direct sequencing in the family members. A homozygous nonsense mutation in exon 4 of HJV (Q312X) was identified in the JH patients and their mother. Three individuals in the family were heterozygous for this mutation. Subsequently, we evaluated the frequency of Q312X mutation in a large population (n=361) without heart failure, using allele-specific real-time PCR assay. No Q312X mutation was detected in this population. In the patients with the homozygous HJV mutation, iron loading revealed high serum ferritin concentration with accompanying elevated transferrin iron saturation. In contrast, ferritin levels were within the normal range in individuals with the heterozygous mutation.
  
  
  CONCLUSIONS
  We found a nonsense mutation in the HJV gene. This mutation elevates ferritin levels and leads to JH associated with severe cardiomyopathy.
authors: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan. ynagayos@kumamoto-u.ac.jp
authors: Yasuhiro
authors: Y
authors: Nagayoshi
authors: Masafumi
authors: M
authors: Nakayama
authors: Satoru
authors: S
authors: Suzuki
authors: Jun
authors: J
authors: Hokamaki
authors: Hideki
authors: H
authors: Shimomura
authors: Kenichi
authors: K
authors: Tsujita
authors: Masaya
authors: M
authors: Fukuda
authors: Takuro
authors: T
authors: Yamashita
authors: Yoshinori
authors: Y
authors: Nakamura
authors: Seigo
authors: S
authors: Sugiyama
authors: Hisao
authors: H
authors: Ogawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D009202:Cardiomyopathies / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D058851:GPI-Linked Proteins; D006432:Hemochromatosis / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; D018389:Codon, Nonsense; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D008565:Membrane Proteins