Whole-exome sequencing for genetic diagnosis of idiopathic liver injury in children.

Autor: Lülecioğlu AA; Department of Molecular Biology and Genetics, Faculty of Science, İhsan Doğramacı Bilkent University, Ankara, Turkey., Yazıcı YY; Department of Molecular Biology and Genetics, Faculty of Science, İhsan Doğramacı Bilkent University, Ankara, Turkey., Baran A; Department of Molecular Biology and Genetics, Faculty of Science, İhsan Doğramacı Bilkent University, Ankara, Turkey., Warasnhe K; Department of Pediatrics, Başkent University Faculty of Medicine, Ankara, Turkey., Beyaz Ş; Department of Immunology and Allergy Diseases, Ankara Bilkent City Hospital, Ankara, Turkey., Aytekin C; Department of Pediatric Immunology, Dr. Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, Ankara, Turkey., Özçay F; Department of Pediatric Gastroenterology and Hepatology, Başkent University Faculty of Medicine, Ankara, Turkey., Aydemir Y; Department of Pediatric Gastroenterology, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey., Barış Z; Department of Pediatric Gastroenterology, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey., Belkaya S; Department of Molecular Biology and Genetics, Faculty of Science, İhsan Doğramacı Bilkent University, Ankara, Turkey.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Jun; Vol. 28 (11), pp. e18485.
DOI: 10.1111/jcmm.18485
Abstrakt: Genome-wide approaches, such as whole-exome sequencing (WES), are widely used to decipher the genetic mechanisms underlying inter-individual variability in disease susceptibility. We aimed to dissect inborn monogenic determinants of idiopathic liver injury in otherwise healthy children. We thus performed WES for 20 patients presented with paediatric-onset recurrent elevated transaminases (rELT) or acute liver failure (ALF) of unknown aetiology. A stringent variant screening was undertaken on a manually-curated panel of 380 genes predisposing to inherited human diseases with hepatobiliary involvement in the OMIM database. We identified rare nonsynonymous variants in nine genes in six patients (five rELT and one ALF). We next performed a case-level evaluation to assess the causal concordance between the gene mutated and clinical symptoms of the affected patient. A genetic diagnosis was confirmed in four rELT patients (40%), among whom two carried novel mutations in ACOX2 or PYGL, and two had previously-reported morbid variants in ABCB4 or PHKA2. We also detected rare variants with uncertain clinical significance in CDAN1, JAG1, PCK2, SLC27A5 or VPS33B in rELT or ALF patients. In conclusion, implementation of WES improves diagnostic yield and enables precision management in paediatric cases of liver injury with unknown aetiology, in particular recurrent hypertransaminasemia.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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