학술논문
Revisiting Exome Data Identified Missed Splice Site Variant of the Asparagine Synthetase ( ASNS ) Gene.
Document Type
Academic Journal
Author
Al-Kasbi G; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.; Al-Murshedi F; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.; Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman.; Al-Futaisi A; Department of Child Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.; Al-Jabry T; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.; Zadjali F; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.; Al-Yahyaee S; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.; Al-Maawali A; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.; Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman.
Source
Publisher: Thieme Country of Publication: Germany NLM ID: 101589859 Publication Model: eCollection Cited Medium: Print ISSN: 2146-4596 (Print) Linking ISSN: 2146460X NLM ISO Abbreviation: J Pediatr Genet Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2146-4596
Abstract
Next-generation sequencing, such as whole-exome sequencing (WES), is increasingly used in the study of Mendelian disorders, yet many are reported as "negative." Inappropriate variant annotation and filtering steps are reasons for missing the molecular diagnosis. Noncoding variants, including splicing mutations, are examples of variants that can be overlooked. Herein, we report a family of four affected newborns, and all presented with severe congenital microcephaly. Initial research WES analysis identified a damaging homozygous variant in NME1 gene as a possible cause of primary microcephaly phenotype in these patients. However, reanalysis of the exome data uncovered a biallelic splice site variant in asparagine synthetase gene which seems to be the possible cause of the phenotype in these patients. This study highlights the importance of revisiting the exome data and the issue of "negative" exome and the afterward approaches to identify and prove new candidate genes.
Competing Interests: Conflict of Interest None declared.
(Thieme. All rights reserved.)
Competing Interests: Conflict of Interest None declared.
(Thieme. All rights reserved.)