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Open Access 01-12-2019 | Hypogonadism | Review

Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review

Authors: Xiaomu Kong, Lingding Xie, Haiqing Zhu, Lulu Song, Xiaoyan Xing, Wenying Yang, Xiaoping Chen

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

Abstract

Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis, arthritis, abnormal skin pigmentation, cardiomyopathy, hypogonadism, and diabetes. Hemojuvelin (HJV) is the causative gene of a rare subtype of HH worldwide. This study aims to systematically review the genotypic and phenotypic spectra of HJV-HH in multiple ethnicities, and to explore the genotype–phenotype correlations. A comprehensive search of PubMed database was conducted. Data were extracted from 57 peer-reviewed original articles including 132 cases with HJV-HH of multiple ethnicities, involving 117 biallelic cases and 15 heterozygotes. Among the biallelic cases, male and female probands of Caucasian ancestry were equally affected, whereas males were more often affected among East Asians (P=1.72×10^-2). Hepatic iron deposition and hypogonadism were the most frequently reported complications. Hypogonadism and arthropathy were more prevalent in Caucasians than in East Asians (P=9.30×10^-3, 1.69×10^-2). Among the recurrent mutations, G320V (45 unrelated cases) and L101P (7 unrelated cases) were detected most frequently and restricted to Caucasians. [Q6H; C321*] was predominant in Chinese patients (6 unrelated cases). I281T (Chinese and Greek), A310G (Brazilian and African American), and R385* (Italian and North African) were reported across different ethnicities. In genotype–phenotype correlation analyses, 91.30% of homozygotes with exon 2-3 mutations developed early-onset HH compared to 66.00% of those with exon 4 mutations (P=2.40×10^-2). Hypogonadism occurred more frequently in homozygotes with missense mutations (72.55%) than in those with nonsense mutations (35.71%; P=2.43×10^-2). Liver biopsy was accepted by more probands with frame-shift or missense mutations (85.71% and 60.78%, respectively) than by those with nonsense mutations (28.57%; P=2.37×10^-2, 3.93×10^-2). The present review suggests that patients’ ethnicity, geographical region, and genetic predisposition should be considered in the diagnosis, prognosis and management of HJV-HH.

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Title: Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review
Authors: Xiaomu Kong
Lingding Xie
Haiqing Zhu
Lulu Song
Xiaoyan Xing
Wenying Yang
Xiaoping Chen
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Hypogonadism
Published in: Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-019-1097-2

At a glance: The STEP trials

Springer Medicine

Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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