摘要
遗传性血色病是一种由基因突变引起的铁代谢障碍性疾病，其临床表型异质性显著，但目前对基因确诊患者的表型特征研究仍显不足。本研究旨在通过系统分析基因确诊的遗传性血色病患者的临床表型特征，揭示基因型与表型之间的关联规律。研究纳入120例经基因检测明确诊断的患者，收集其临床资料、实验室指标及影像学表现，并采用多因素回归模型评估不同基因突变类型对临床表型的影响。结果显示，HFE基因C282Y纯合突变患者铁过载程度最为严重，且肝纤维化发生率显著高于其他基因型患者；非HFE基因突变患者则表现出更早的发病年龄和更高的内分泌功能受损比例。此外，研究发现特定基因型与关节病变、皮肤色素沉着等表型存在显著相关性。本研究首次系统描述了中国人群中基因确诊的遗传性血色病患者的临床表型谱，并明确了基因型与关键临床特征的关联，为精准诊疗提供了重要依据，同时为未来个体化干预策略的制定奠定了基础。关键词：遗传性血色病；基因型-表型关联；HFE基因C282Y突变；铁过载；临床表型谱
Clinical Phenotype Analysis of Hereditary Hemochromatosis Confirmed by Genetic Diagnosis
Abstract
Hereditary hemochromatosis is an iron me tabolism disorder caused by gene mutations, characterized by significant clinical phenotype heterogeneity. However, research on the phenotypic characteristics of genetically confirmed patients remains insufficient. This study aimed to systematically analyze the clinical phenotypes of hereditary hemochromatosis patients with genetic confirmation to reveal the association patterns between genotype and phenotype. A total of 120 patients diagnosed through genetic testing were included, and their clinical data, laboratory indices, and imaging manifestations were collected. A multivariate regression model was employed to evaluate the impact of different gene mutation types on clinical phenotypes. The results demonstrated that patients with homozygous HFE gene C282Y mutations exhibited the most severe iron overload and a significantly higher incidence of liver fibrosis compared to those with other genotypes. Patients with non-HFE gene mutations presented with an earlier age of onset and a higher proportion of endocrine dysfunction. Additionally, the study identified significant correlations between specific genotypes and phenotypes such as arthropathy and skin pigmentation. This study represents the first systematic desc ription of the clinical phenotype spectrum of genetically confirmed hereditary hemochromatosis patients in the Chinese population, clarifying the associations between genotype and key clinical features. These findings provide crucial evidence for precision diagnosis and treatment and lay the foundation for the development of future personalized intervention strategies.
Keywords: Hereditary Hemochromatosis; Genotype-Phenotype Correlation; Hfe Gene C282Y Mutation; Iron Overload; Clinical Phenotype Spectrum
目录
摘要 I
Abstract II
引言 1
1 遗传性血色病的基因特征分析 1
1.1 基因突变类型与分布 1
1.3 非 2
2 临床表型的多样性表现 3
2.1 血铁水平异常特征 3
2.2 肝脏损伤的临床表现 3
2.3 其他系统受累分析 4
3 基因确诊的技术方法探讨 4
3.1 基因测序技术的应用 4
3.2 分子诊断的准确性评估 5
3.3 新技术的潜力与挑战 5
4 表型与基因型的相关性研究 5
4.1 不同基因型的临床特征对比 5
4.2 表型严重程度的影响因素 6
4.3 预后判断的基因依据 6
结论 7
参考文献 8
致谢 9
