title: Juvenile Hemochromatosis, Genetic Study and Long-term Follow up after Therapy.
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.
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoud M
authors.initials: MM
authors.lastname: Malekzadeh
authors.affiliation: Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran Iran.
authors.forename: Amir Reza
authors.initials: AR
authors.lastname: Radmard
authors.affiliation: Section of Gastroenterology, Department of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nouroozi
authors.affiliation: Division of Genetic Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Akbari
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Marzie
authors.initials: M
authors.lastname: Amini
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behrooz
authors.initials: B
authors.lastname: Navabakhsh
authors.affiliation: Division of Internal Medicine and Center for Hemochromatosis, University Hospital of Modena Policlinico di Modena Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Caleffi
authors.affiliation: Division of Internal Medicine and Center for Hemochromatosis, University Hospital of Modena Policlinico di Modena Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Pietrangelo
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
keywords: Genetic Study; Hemojuvelin Mutation; Iran; Juvenile Hemochromatosis