Diagnostic Uptake of Targeted Sequencing in Adults With Steatotic Liver Disease and a Suspected Genetic Contribution

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-02-13 DOI:10.1111/liv.70010

Luisa Ronzoni, Serena Pelusi, Vittoria Moretti, Francesco Malvestiti, Hadi Eidgah Torghabehei, Oveis Jamialahmadi, Jessica Rondena, Cristiana Bianco, Giulia Periti, Maria Rosaria De Filippo, Stefano Romeo, Daniele Prati, Luca Valenti

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Abstract

Background and Aims

In patients with steatotic liver diseases (SLD), genetic factors may account for severe liver involvement despite mild or absence of triggering factors or a strong family history. Aim of this study was to examine the diagnostic uptake of targeted sequencing (TS), covering both coding and non-coding regions, of a broad panel of 82 liver and lipid metabolism genes in patients with unexplained SLD.

Methods

We enrolled 49 adult patients with SLD and a suspected genetic contribution. Genetic variants were detected through a customised TS panel, whereas the contribution of common genetic variation to the individual susceptibility to SLD was captured by a polygenic risk score (SLD-PRS).

Results

A diagnosis of rare Mendelian disorder was established in 11 patients (22%), independently of age or family history. Rare variants possibly contributing to clinical phenotype were detected in additional 29 patients (59%). Increased SLD-PRS values were detected in 17 patients (35%), enabling an increase in diagnostic uptake of 24%, especially in those without a strong family history (p = 0.03). Genetic diagnosis allowed refinement of clinical management in 23 (47%) patients.

Conclusions

The diagnostic uptake of TS was 22% for Mendelian disorder and 59% for possible contribution to clinical phenotype in selected adult patients with SLD. Evaluation of common variants, as captured by SLD-PRS, yields complementary information increasing the overall utility of the genetic examination.

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成人脂肪变性肝病的靶向测序诊断和可疑的遗传贡献

背景和目的在脂肪变性肝病（SLD）患者中，遗传因素可能导致严重的肝脏受累，尽管轻微或没有触发因素或有强烈的家族史。本研究的目的是检查不明原因SLD患者82个肝脏和脂质代谢基因的靶向测序（TS）的诊断摄取，包括编码区和非编码区。方法我们招募了49例SLD和疑似遗传因素的成年患者。通过定制的TS面板检测遗传变异，而通过多基因风险评分（SLD- prs）捕获常见遗传变异对个体对SLD易感性的贡献。结果11例（22%）患者被诊断为罕见孟德尔障碍，与年龄或家族史无关。在另外29例（59%）患者中检测到可能导致临床表型的罕见变异。在17例（35%）患者中检测到SLD-PRS值升高，使诊断摄取增加24%，特别是在没有强烈家族史的患者中（p = 0.03）。遗传诊断使23例（47%）患者的临床管理得到改善。结论：在选定的成年SLD患者中，孟德尔障碍的TS诊断吸收率为22%，可能对临床表型有贡献的TS诊断吸收率为59%。由SLD-PRS捕获的常见变异的评估产生了补充信息，增加了遗传检查的总体效用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.