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Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review
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 subty...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615163/ https://www.ncbi.nlm.nih.gov/pubmed/31286966 http://dx.doi.org/10.1186/s13023-019-1097-2 |
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author | Kong, Xiaomu Xie, Lingding Zhu, Haiqing Song, Lulu Xing, Xiaoyan Yang, Wenying Chen, Xiaoping |
author_facet | Kong, Xiaomu Xie, Lingding Zhu, Haiqing Song, Lulu Xing, Xiaoyan Yang, Wenying Chen, Xiaoping |
author_sort | Kong, Xiaomu |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-019-1097-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6615163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66151632019-07-18 Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review Kong, Xiaomu Xie, Lingding Zhu, Haiqing Song, Lulu Xing, Xiaoyan Yang, Wenying Chen, Xiaoping Orphanet J Rare Dis Review 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-019-1097-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-08 /pmc/articles/PMC6615163/ /pubmed/31286966 http://dx.doi.org/10.1186/s13023-019-1097-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Kong, Xiaomu Xie, Lingding Zhu, Haiqing Song, Lulu Xing, Xiaoyan Yang, Wenying Chen, Xiaoping Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review |
title | Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review |
title_full | Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review |
title_fullStr | Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review |
title_full_unstemmed | Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review |
title_short | Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review |
title_sort | genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615163/ https://www.ncbi.nlm.nih.gov/pubmed/31286966 http://dx.doi.org/10.1186/s13023-019-1097-2 |
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