Lipiński Patryk, Ciara Elżbieta, Jurkiewicz Dorota, Pollak Agnieszka, Wypchło Maria, Płoski Rafał, Cielecka-Kuszyk Joanna, Socha Piotr, Pawłowska Joanna, Jankowska Irena
Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.
Front Pediatr. 2020 Jul 24;8:414. doi: 10.3389/fped.2020.00414. eCollection 2020.
To evaluate the clinical utility of panel-based NGS in the diagnostic approach of monogenic cholestatic liver diseases. Patients with diagnosis of chronic cholestatic liver disease of an unknown etiology underwent NGS of targeted genes panel. Group 1 included five patients (prospectively recruited) hospitalized from January to December 2017 while group 2 included seventeen patients (retrospectively recruited) hospitalized from 2010 to 2017 presenting with low-GGT PFIC phenotype (group 2a, 11 patients) or indeterminant cholestatic liver cirrhosis (group 2b, 6 patients). Among 22 patients enrolled into the study, 21 various pathogenic variants (including 11 novel) in 5 different genes (including ) were identified. The molecular confirmation was obtained in 15 out of 22 patients (68%). In group 1, two out of five patients presented with low-GGT cholestasis, and were diagnosed with BSEP deficiency. Out of three patients presenting with high-GGT cholestasis, one patient was diagnosed with PFIC-3, and the remaining two were not molecularly diagnosed. In group 2a, seven out of eleven patients, were diagnosed with BSEP deficiency and two with TJP-2 deficiency. In group 2b, three out of six patients were molecularly diagnosed; one with PFIC-3, one with CYP27A1 deficiency, and one with DGUOK deficiency. Panel-based NGS appears to be a very useful tool in diagnosis of monogenic cholestatic liver disorders in cases when extrahepatic causes have been primarily excluded. NGS presented the highest diagnosis rate to identify the molecular background of cholestatic liver diseases presenting with a low-GGT PFIC phenotype.
评估基于基因panel的二代测序（NGS）在单基因胆汁淤积性肝病诊断方法中的临床应用价值。病因不明的慢性胆汁淤积性肝病患者接受了靶向基因panel的NGS检测。第1组包括2017年1月至12月住院的5例患者（前瞻性招募），而第2组包括2010年至2017年住院的17例患者（回顾性招募），这些患者表现为低γ-谷氨酰转移酶（GGT）的进行性家族性肝内胆汁淤积症（PFIC）表型（第2a组，11例患者）或不确定的胆汁淤积性肝硬化（第2b组，6例患者）。在纳入该研究的22例患者中，在5个不同基因（包括 ）中鉴定出21种不同的致病变异（包括11种新变异）。22例患者中有15例（68%）获得了分子确诊。在第1组中，5例患者中有2例表现为低GGT胆汁淤积，被诊断为BSEP缺乏症。在3例表现为高GGT胆汁淤积的患者中，1例被诊断为PFIC-3，其余2例未得到分子诊断。在第2a组中，11例患者中有7例被诊断为BSEP缺乏症，2例被诊断为TJP-2缺乏症。在第2b组中，6例患者中有3例得到分子诊断；1例为PFIC-3，1例为CYP27A1缺乏症，1例为DGUOK缺乏症。在主要排除肝外病因的情况下，基于基因panel的NGS似乎是诊断单基因胆汁淤积性肝病的非常有用的工具。NGS在识别表现为低GGT PFIC表型的胆汁淤积性肝病的分子背景方面具有最高的诊断率。
