A Juvenile Hemochromatosis Patient Homozygous for a Novel Deletion of cDNA Nucleotide 81 of Hemojuvelin

2006 ◽  
Vol 115 (1-2) ◽  
pp. 123-127 ◽  
Author(s):  
Pauline Lee ◽  
Kittichai Promrat ◽  
Carol Mallette ◽  
Maura Flynn ◽  
Ernest Beutler
Keyword(s):  
Juvenile Hemochromatosis ◽  
Cdna Nucleotide

Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4669-4671 ◽  
Author(s):  
Pauline L. Lee ◽  
Ernest Beutler ◽  
Sreenivas V. Rao ◽  
James C. Barton
Keyword(s):  
Early Onset ◽  
Storage Disease ◽  
Causative Gene ◽  
Gene Encoding ◽  
Iron Storage ◽  
Hypogonadotrophic Hypogonadism ◽  
Juvenile Hemochromatosis ◽  
Genetic Abnormalities

AbstractJuvenile hemochromatosis is an early-onset form of iron storage disease characterized by hypogonadotrophic hypogonadism and cardiomyopathy. Recently, the putative causative gene (LOC148738) encoding a protein designated hemojuvelin was cloned. The previously proposed designation of this gene as HFE2 is contrary to established convention, because it is not a member of the HFE family. We suggest that it be designated HJV. We sequenced this gene in members of 2 previously reported kinships that manifest typical juvenile hemochromatosis. In one kinship, 2 previously undescribed mutations of HJV were identified, c.238T>C (C80R) and c.302T>C (L101P). In the second kinship, 2 previously identified mutations, G320V and I222N, were found. These studies confirm that mutations in HJV cause juvenile hemochromatosis. (Blood. 2004;103:4669-4671)

scholarly journals Juvenile Hemochromatosis: A Case Report and Review of the Literature

2020 ◽  
Vol 13 (8) ◽  
pp. 195
Author(s):  
Akiyoshi Takami ◽  
Yasuaki Tatsumi ◽  
Katsuhisa Sakai ◽  
Yasumichi Toki ◽  
Katsuya Ikuta ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Age Of Onset ◽  
Relevant Literature ◽  
Autosomal Recessive Disorder ◽  
Age Difference ◽  
Outpatient Basis ◽  
Review Of The Literature ◽  
Hepcidin Expression ◽  
Juvenile Hemochromatosis ◽  
First Time

Juvenile hemochromatosis (JH), type 2A hemochromatosis, is a rare autosomal recessive disorder of systemic iron overload due to homozygous mutations of HJV (HFE2), which encodes hemojuvelin, an essential regulator of the hepcidin expression, causing liver fibrosis, diabetes, and heart failure before 30 years of age, often with fatal outcomes. We report two Japanese sisters of 37 and 52 years of age, with JH, who showed the same homozygous HJV I281T mutation and hepcidin deficiency and who both responded well to phlebotomy on an outpatient basis. When all reported cases of JH with homozygous HJV mutations in the relevant literature were reviewed, we found—for the first time—that JH developed in females and males at a ratio of 3:2, with no age difference in the two groups. Furthermore, we found that the age of onset of JH may depend on the types of HJV mutations. In comparison to patients with the most common G320V/G320V mutation, JH developed earlier in patients with L101P/L101P or R385X/R385X mutations and later in patients with I281T/I281T mutations.

scholarly journals Cytochrome P45OCMF cDNA: nucleotide sequence of P45OCMF1b

1989 ◽  
Vol 17 (15) ◽  
pp. 6407-6407 ◽  
Author(s):  
Nobuhiro Eshida ◽  
Chikako Inuzuka ◽  
Yasunori Tawaragi ◽  
Osamu Sugita ◽  
Hiroshi Nakazato ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Cdna Nucleotide Sequence ◽  
Cdna Nucleotide

Immunoassay for human serum hepcidin

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4292-4297 ◽  
Author(s):  
Tomas Ganz ◽  
Gordana Olbina ◽  
Domenico Girelli ◽  
Elizabeta Nemeth ◽  
Mark Westerman
Keyword(s):  
Healthy Volunteers ◽  
Immunosorbent Assay ◽  
Limit Of Detection ◽  
Deficiency Anemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Reactive Protein ◽  
Transient Rise ◽  
Juvenile Hemochromatosis ◽  
Serum Hepcidin ◽  
Clinical Conditions

Abstract We developed and validated the first serum enzyme-linked immunosorbent assay for hepcidin, the principal iron-regulatory hormone that has been very difficult to measure. In healthy volunteers, the 5% to 95% range of hepcidin concentrations was 29 to 254 ng/mL in men (n = 65) and 17 to 286 ng/mL in women (n = 49), with median concentrations 112 versus 65 (P < .001). The lower limit of detection was 5 ng/mL. Serum hepcidin concentrations in 24 healthy subjects correlated well with their urinary hepcidin (r = 0.82). Serum hepcidin appropriately correlated with serum ferritin (r = 0.63), reflecting the regulation of both proteins by iron stores. Healthy volunteers showed a diurnal increase of serum hepcidin at noon and 8 pm compared with 8 am, and a transient rise of serum hepcidin in response to iron ingestion. Expected alterations in hepcidin levels were observed in a variety of clinical conditions associated with iron disturbances. Serum hepcidin concentrations were undetectable or low in patients with iron deficiency anemia (ferritin < 10 ng/mL), iron-depleted HFE hemochromatosis, and juvenile hemochromatosis. Serum hepcidin concentrations were high in patients with inflammation (C-reactive protein > 10 mg/dL), multiple myeloma, or chronic kidney disease. The new serum hepcidin enzyme-linked immunosorbent assay yields accurate and reproducible measurements that appropriately reflect physiologic, pathologic, and genetic influences, and is informative about the etiology of iron disorders.

Full-length cDNA nucleotide sequence of a serologically undetectable YLLA-DQA1allele: HLA-DQA1*“LA”

1997 ◽  
Vol 50 (4) ◽  
pp. 334-339 ◽  
Author(s):  
N. M. Lardy ◽  
N. Otting ◽  
A. R. Horst ◽  
R. E. Bontrop ◽  
L. P. Waal
Keyword(s):  
Nucleotide Sequence ◽  
Full Length ◽  
Full Length Cdna ◽  
Cdna Nucleotide Sequence ◽  
Hla Dqa1 ◽  
Cdna Nucleotide

scholarly journals Expression of Human Hemojuvelin (HJV) Is Tightly Regulated by Two Upstream Open Reading Frames in HJV mRNA That Respond to Iron Overload in Hepatic Cells

2015 ◽  
Vol 35 (8) ◽  
pp. 1376-1389 ◽  
Author(s):  
Cláudia Onofre ◽  
Filipa Tomé ◽  
Cristina Barbosa ◽  
Ana Luísa Silva ◽  
Luísa Romão
Keyword(s):  
Iron Overload ◽  
Iron Homeostasis ◽  
Open Reading Frames ◽  
Initiation Factor ◽  
Translational Repression ◽  
Translational Efficiency ◽  
Hepatic Cells ◽  
Juvenile Hemochromatosis ◽  
Upstream Open Reading Frames ◽  
Reading Frames

The gene encoding human hemojuvelin (HJV) is one of the genes that, when mutated, can cause juvenile hemochromatosis, an early-onset inherited disorder associated with iron overload. The 5′ untranslated region of the human HJV mRNA has two upstream open reading frames (uORFs), with 28 and 19 codons formed by two upstream AUGs (uAUGs) sharing the same in-frame stop codon. Here we show that these uORFs decrease the translational efficiency of the downstream main ORF in HeLa and HepG2 cells. Indeed, ribosomal access to the main AUG is conditioned by the strong uAUG context, which results in the first uORF being translated most frequently. The reach of the main ORF is then achieved by ribosomes that resume scanning after uORF translation. Furthermore, the amino acid sequences of the uORF-encoded peptides also reinforce the translational repression of the main ORF. Interestingly, when iron levels increase, translational repression is relieved specifically in hepatic cells. The upregulation of protein levels occurs along with phosphorylation of the eukaryotic initiation factor 2α. Nevertheless, our results support a model in which the increasing recognition of the main AUG is mediated by a tissue-specific factor that promotes uORF bypass. These results support a tight HJV translational regulation involved in iron homeostasis.

Juvenile hemochromatosis due to homozygosity for the G320V mutation in theHJVgene with fatal outcome

2009 ◽  
Vol 76 (5) ◽  
pp. 493-495 ◽  
Author(s):  
Kai Brakensiek ◽  
Christine Fegbeutel ◽  
Madeleine Mälzer ◽  
Martin Strüber ◽  
Hans Kreipe ◽  
...  
Keyword(s):  
Fatal Outcome ◽  
Juvenile Hemochromatosis

Molecular Mechanism of Hepcidin Deficiency in a Patient with Juvenile Hemochromatosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3194-3194
Author(s):  
Alexandra Rideau ◽  
Bastien Mangeat ◽  
Thomas Matthes ◽  
Didier Trono ◽  
Photis Beris
Keyword(s):  
Translation Initiation ◽  
Consensus Sequence ◽  
Protein Translation ◽  
Translation Initiation Site ◽  
Wild Type ◽  
Gfp Expression ◽  
Translational Initiation ◽  
Coding Sequence ◽  
Mammalian Expression ◽  
Juvenile Hemochromatosis

Abstract In eukaryotes protein translation is initiated at an AUG codon typically located within a so-called Kozak sequence (GCCRCC AUG G), a motif that presumably promotes the correct positioning of the mRNA in the ribosome. Recently, we described a patient suffering from juvenile hemochromatosis resulting from a lack of hepcidin production (Blood;15 June 2004; Epub ahead of print). We further revealed that this defect coincided with a G-to-A point mutation at position +14 of the 5′untranslated region (5′UTR) of the HAMP gene. This nucleotide change led to the creation of an ATG codon, out of frame with the physiological pre-hepcidin initiator located at positions +39-41. We speculated that this new ATG, which was embedded within a Kozak consensus sequence, acted as an aberrant translation initiation site that precluded hepcidin synthesis. In order to verify this hypothesis, we cloned in a mammalian expression vector the wild-type and mutant HAMP 5′UTR upstream of a modified EGFP cDNA, replacing the EGFP ATG by the HAMP physiological initiation codon. The resulting vectors were transfected into 293T cells. Presence of the additional ATG in the HAMP 5′UTR led to a 93 % decrease in GFP expression compared with wild-type. To confirm that this effect resulted from aberrant translation initiation at this site, a one-nucleotide deletion was introduced at the very 5′ end of the EGFP coding sequence, in order to place it in frame with the mutant HAMP 5′UTR proximal ATG (GTG in the wild-type sequence). This restored GFP expression to levels obtained when its coding sequence was in frame with the physiological hepcidin ATG of a wild-type HAMP 5′UTR. Our results very strongly suggest that the G to A mutation at position +14 of the HAMP gene 5′UTR blocks hepcidin production by inducing aberrant translational initiation of the pre-hepcidin mRNA. Whether a stable protein is synthesized from the mutated HAMP mRNA, which does not contain a stop codon in frame with the +14 AUG, remains to be determined. It is however unlikely that such protein contributes to the pathology observed in our patient, since the two other cases of hepcidin deficiency reported so far exhibit the same phenotype as our patient in spite of harbouring different mutations in the HAMP gene.

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