Article

Allele frequencies of hemojuvelin gene ( HJV ) I222N and G320V missense mutations in white and African American subjects from the general Alabama population

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
BMC Medical Genetics (Impact Factor: 2.45). 12/2004; 5. DOI: 10.1186/1471-2350-5-29
Source: DOAJ

ABSTRACT Background
Homozygosity or compound heterozygosity for coding region mutations of the hemojuvelin gene (HJV) in whites is a cause of early age-of-onset iron overload (juvenile hemochromatosis), and of hemochromatosis phenotypes in some young or middle-aged adults. HJV coding region mutations have also been identified recently in African American primary iron overload and control subjects. Primary iron overload unexplained by typical hemochromatosis-associated HFE genotypes is common in white and black adults in Alabama, and HJV I222N and G320V were detected in a white Alabama juvenile hemochromatosis index patient. Thus, we estimated the frequency of the HJV missense mutations I222N and G320V in adult whites and African Americans from Alabama general population convenience samples.

Methods
We evaluated the genomic DNA of 241 Alabama white and 124 African American adults who reported no history of hemochromatosis or iron overload to detect HJV missense mutations I222N and G320V using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Analysis for HJV I222N was performed in 240 whites and 124 African Americans. Analysis for HJV G320V was performed in 241 whites and 118 African Americans.

Results
One of 240 white control subjects was heterozygous for HJV I222N; she was also heterozygous for HFE C282Y, but had normal serum iron measures and bone marrow iron stores. HJV I222N was not detected in 124 African American subjects. HJV G320V was not detected in 241 white or 118 African American subjects.

Conclusions
HJV I222N and G320V are probably uncommon causes or modifiers of primary iron overload in adult whites and African Americans in Alabama. Double heterozygosity for HJV I222N and HFE C282Y may not promote increased iron absorption.

1 Follower
 · 
115 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There has been a large increase in data on the genetic causes of iron accumulation. In addition, there is a growing body of literature on the significance of iron in liver biopsy specimens obtained for staging and grading chronic liver disease. In this review, the current literature is discussed with a focus on aspects that are most relevant to the practice of surgical pathology.
    Advances in anatomic pathology 07/2011; 18(4):306-17. DOI:10.1097/PAP.0b013e318220fba0 · 3.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: most hereditary hemochromatosis (HH) patients are homozygous for the p.C282Y mutation in the HFE gene. Some studies reported that HH phenotypic expression could be modulated by genetic factors such as HJV and HAMP gene mutations. the aims of this study were to identify HJV and HAMP mutations and to analyze their impact on HH phenotype in non-p.C282Y homozygous individuals. Methods: Twenty-four Brazilian patients with primary iron overload and non-p.C282Y homozygous genotype (transferrin saturation >50% in women and >60% in men and absence of secondary causes) were selected. Subsequent bidirectional sequencing of the HJV and HAMP exons was performed. sequencing revealed a substitution in heterozygosis, c.929C > G, which corresponds to p.A310G polymorphism in HJV exon 4 (rs7540883). In the same gene, in another individual, an IVS1-36C > G intronic variant was detected in heterozygosis. In the HAMP gene, an IVS3 + 42G > A intronic variant was identified. There were six (25.0%) patients carrying a heterozygous genotype for the HFE p.C282Y and nine (37.5%) patients carrying a heterozygous genotype for the HFE p.H63D. HJV p.A310G polymorphism and two intronic variants were found, but none of these alterations were associated with digenic inheritance with the HFE gene. Our data indicate that HJV and HAMP functional mutations are not frequent in these patients.
    Genetic Testing and Molecular Biomarkers 11/2010; 14(6):803-6. DOI:10.1089/gtmb.2010.0056 · 1.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND Hereditary hemochromatosis (HH) is a very rare disease in Iran and reported cases are all negative for HFE mutation. We report a family affected by severe juvenile hemochromatosis (JH) with a detailed molecular study of the family members. METHODS We studied a pedigree with siblings affected by juvenile HH and followed them for 3 years. Microsatellite and gene sequencing analysis was performed for all family members. RESULTS Two siblings (the proband and his sister, aged 26 and 30 years, respectively) were found to have clinical findings of JH. The proband's brother, who presented with hyperpigmentation, died of probable JH at the age of 24 years. Gene sequencing analysis showed that the proband has a homozygote c.265T>C (p.C89R) HJV mutation + a heterozygote c.884T>C (p.V295A) mutation of HFE. The affected proband's sister presented with the same HJV c.265T>C (p.C89R) homozygote mutation. In addition, we found the HJV c.98-6C>G polymorphic variant in both the sister and proband (homozygote). Sequencing of hepcidin (HAMP), TfR2, and FPN revealed no mutation. CONCLUSION We have shown that molecular analysis of the HH related gene is a powerful tool for reliable diagnosis of JH and, in conjunction with magnetic resonance imaging (MRI) and noninvasive liver stiffness measurement by elastography, is adequate tool for management and follow up of HH.
    04/2014; 6(2):87-92.

Full-text (3 Sources)

Download
0 Downloads
Available from
Apr 6, 2015