Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis.
Juvenile or type 2 hemochromatosis (JH) is transmitted as a recessive trait that leads to severe iron overload and organ damage typically before age 30 years. Linkage to a locus on chromosome 1q has been found in most patients with JH. The recently identified causal gene encodes hemojuvelin, a protein with a proposed crucial role in iron metabolism. A second, rare type of JH, with clinical expression identical to the 1q-linked form, is due to inactivation of hepcidin, the key regulator of iron homeostasis. Here we report the spectrum of mutations of the hemojuvelin gene (HJV) in 34 patients who did not show hepcidin mutations. This represents the largest cohort of patients with JH collected worldwide. We identified 17 different (16 novel) mutations of HJV, both at the homozygous and at the compound heterozygous state. Mutations either generate premature termination codons or were missense substitutions, affecting highly conserved residues, relevant to the protein structure and/or function.
Dipartimento di Patologia Generale, II Università di Napoli, Italy.
Carmela
C
Lanzara
Antonella
A
Roetto
Filomena
F
Daraio
Silvain
S
Rivard
Romina
R
Ficarella
Hervey
H
Simard
Timothy M
TM
Cox
Mario
M
Cazzola
Alberto
A
Piperno
Anne-Paule
AP
Gimenez-Roqueplo
Paola
P
Grammatico
Stefano
S
Volinia
Paolo
P
Gasparini
Clara
C
Camaschella
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D058851:GPI-Linked Proteins; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation
D058851:GPI-Linked Proteins; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D008565:Membrane Proteins