To B(enign) or Not to B: functionalisation of variant in a mild form of argininosuccinate lyase deficiency identified through newborn screening.

Autor:	Heng TYJ; Department of Paediatrics, KK Women's and Children's Hospital., Ow JR; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)., Koh AL; Genetics Service, Department of Paediatrics, KK Women's and Children's Hospital.; SingHealth Duke-NUS Paediatric Academic Clinical Programme, Duke-NUS Medical School., Lim JSC; Biochemical Genetics and National Expanded Newborn Screening, Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital., Ong CBK; Department of Nutrition and Dietetics, KK Women's and Children's Hospital., Goh JCY; Division of Nursing - Nursing Clinical Services, KK Women's and Children's Hospital., Lim JY; Genetics Service, Department of Paediatrics, KK Women's and Children's Hospital., Chiou FK; SingHealth Duke-NUS Paediatric Academic Clinical Programme, Duke-NUS Medical School.; Gastroenterology, Hepatology & Nutrition Service, Department of Paediatrics, KK Women's and Children's Hospital., Jamuar SS; Genetics Service, Department of Paediatrics, KK Women's and Children's Hospital.; SingHealth Duke-NUS Paediatric Academic Clinical Programme, Duke-NUS Medical School.; SingHealth Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Republic of Singapore.
Jazyk:	angličtina
Zdroj:	Clinical dysmorphology [Clin Dysmorphol] 2024 Jan 01; Vol. 33 (1), pp. 43-49. Date of Electronic Publication: 2023 Oct 13.
DOI:	10.1097/MCD.0000000000000475
Abstrakt:	Argininosuccinate lyase (ASL) deficiency is an autosomal recessive disorder of the urea cycle with a diverse spectrum of clinical presentation that is detectable in newborn screening. We report an 8-year-old girl with ASL deficiency who was detected through newborn screening and was confirmed using biochemical and functional assay. She is compound heterozygous for a likely pathogenic variant NM_000048.4(ASL):c.283C>T (p.Arg95Cys) and a likely benign variant NM_000048.4(ASL): c.1319T>C (p.Leu440Pro). Functional characterisation of the likely benign genetic variant in ASL was performed. Genomic sequencing was performed on the index patient presenting with non-specific symptoms of poor feeding and lethargy and shown to have increased serum and urine argininosuccinic acid. Functional assay using HEK293T cell model was performed. ASL enzymatic activity was reduced for Leu440Pro. This study highlights the role of functional testing of a variant that may appear benign in a patient with a phenotype consistent with ASL deficiency, and reclassifies NM_000048.4(ASL): c.1319T>C (p.Leu440Pro) variant as likely pathogenic. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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