International Journal of Molecular Sciences, 2012-02, Vol.13 (2), p.1497-1511
2012
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- Autor(en) / Beteiligte
- Titel
- Molecular diagnostic and pathogenesis of hereditary hemochromatosis
- Ist Teil von
- International Journal of Molecular Sciences, 2012-02, Vol.13 (2), p.1497-1511
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2012
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp) should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms13021497Titel-ID: cdi_doaj_primary_oai_doaj_org_article_719e933473244ed9a65d9ae251c2be8c
- Format
- –
- Schlagworte
- Amino Acid Substitution, Arthritis, Cardiomyopathy, Diabetes mellitus, Ferritin, Genetic screening, Genotypes, Heart, Hemochromatosis, Hemochromatosis - diagnosis, Hemochromatosis - genetics, Hemochromatosis - metabolism, Hemochromatosis - pathology, Hemochromatosis Protein, Hepcidin, Hepcidins - genetics, Hepcidins - metabolism, Hereditary diseases, Heterozygosity, HFE, HFE protein, high-resolution melting, Histocompatibility Antigens Class I - genetics, Histocompatibility Antigens Class I - metabolism, HJV, Homeostasis, Humans, Iron, Liver, Membrane Proteins - genetics, Membrane Proteins - metabolism, molecular diagnostic, Mutation, Missense, Pathology, Molecular - methods, Pigmentation, primary iron overload, Receptors, Transferrin - genetics, Receptors, Transferrin - metabolism, Review, Reviews, Therapeutic applications, Transferrin receptors