Moral Kenan, Kayhan Gülsüm, Duzenli Tarik, Sari Sinan, Cindoruk Mehmet, Ekmen Nergiz
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gazi University, Ankara 06560, Turkey.
Department of Medical Genetics, Gazi University, Ankara 06560, Turkey.
Diagnostics (Basel). 2025 Aug 11;15(16):2010. doi: 10.3390/diagnostics15162010.
The etiology of liver disease remains unidentified in approximately 30% of patients, presenting a persistent diagnostic challenge. While whole-exome sequencing (WES) is well established for identifying rare genetic conditions in pediatric populations, its utility in adult hepatology is less defined. This study aimed to evaluate the diagnostic value of WES in adults with unexplained liver disorder. Fifty-three Turkish adult patients with idiopathic liver disease underwent a comprehensive clinical evaluation and WES at Gazi University Ankara in 2024-2025. The cohort included individuals with idiopathic cholestasis (6/53, 11%), hepatic steatosis (28/53, 53%), unexplained elevated liver enzymes (12/53, 23%), and cryptogenic cirrhosis (7/53, 13%). All patients had inconclusive results from prior standard investigations. ES yielded a definitive molecular diagnosis in 11% (6/53) of cases. Definitive diagnoses were distributed across the following disease categories: idiopathic cholestasis ( = 1), hepatic steatosis ( = 1), elevated liver enzymes ( = 2), and cryptogenic cirrhosis ( = 2). Pathogenic variants were detected in the , , , , and genes. One patient was identified with mosaic Turner syndrome. This study highlights the role of rare genetic variants in the etiology of unexplained liver disease in adults. Integrating whole-exome sequencing into hepatology practice can uncover novel disease mechanisms and improve diagnostic yield, informing more precise patient care.
约30%的肝病患者病因仍不明，这带来了持续的诊断挑战。虽然全外显子组测序（WES）在识别儿科人群中的罕见遗传病方面已得到充分确立，但其在成人肝病学中的效用尚不太明确。本研究旨在评估WES在不明原因肝病成人患者中的诊断价值。2024年至2025年，53名患有特发性肝病的土耳其成年患者在安卡拉加齐大学接受了全面的临床评估和WES检测。该队列包括特发性胆汁淤积患者（6/53，11%）、肝脂肪变性患者（28/53，53%）、不明原因肝酶升高患者（12/53，23%）和隐源性肝硬化患者（7/53，13%）。所有患者先前的标准检查结果均不明确。WES在11%（6/53）的病例中得出了明确的分子诊断。明确的诊断分布在以下疾病类别中：特发性胆汁淤积（=1）、肝脂肪变性（=1）、肝酶升高（=2）和隐源性肝硬化（=2）。在 、 、 、 和 基因中检测到了致病变异。一名患者被诊断为嵌合型特纳综合征。本研究强调了罕见基因变异在成人不明原因肝病病因中的作用。将全外显子组测序纳入肝病学实践可以揭示新的疾病机制，提高诊断率，为更精确的患者护理提供依据。
