Reanalysis of exome sequencing data reveals a treatable neurometabolic origin in two previously undiagnosed siblings with neurodevelopmental disorder.

Autor: Susgun S; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.; Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey.; Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey., Kesim Y; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.; Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey.; Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brooks University, Oxford, UK., Khalilov D; Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Sirin NG; Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Gezegen H; Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Salman B; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.; Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey., Yucesan E; Department of Neurogenetics, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey., Gokcay G; Department of Pediatrics, Division of Pediatric Nutrition and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Korbeyli HK; Department of Pediatrics, Division of Pediatric Nutrition and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Balci MC; Department of Pediatrics, Division of Pediatric Nutrition and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Iseri SAU; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. sibel.ugur@istanbul.edu.tr., Baykan B; Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Bebek N; Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Jazyk: angličtina
Zdroj: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology [Neurol Sci] 2023 Jul; Vol. 44 (7), pp. 2527-2540. Date of Electronic Publication: 2023 Feb 28.
DOI: 10.1007/s10072-023-06699-8
Abstrakt: Neurodevelopmental disorders (NDDs) have broad heterogeneity both clinically and genetically. Inborn errors of metabolism can be one of the reasons of neurodevelopmental disruption causing specific NDDs. Although there is tremendous advance in molecular identification via next-generation sequencing (NGS), there are still many unsolved patients with NDD. Reanalysis of NGS data with different pipelines can at least partially accomplish this challenge. Herein, we report clinic and genetic components of an adult sib-pair with an undiagnosed NDD condition, which has been solved through reanalysis of whole-exome sequencing (WES). Parallel analysis of SNP-based genotyping and WES was performed to focus on variants only in loci with positive logarithm of the odds scores. WES data was analyzed through three different pipelines with two distinct bed files. Reanalysis of WES data led us to detect a homozygous FOLR1 variant (ENST00000393676.5:c.610C > T, p.(Arg204Ter), rs952165627) in the affected sib-pair. Surprisingly, the variant could not be detected in the first analysis as the variant region is not included in the first bed file which may frequently be used. Biochemical tests of CSF have confirmed the genetic analysis, CSF folic acid levels were detected low in sib-pair, and intravenous folinic acid treatment improved the disease course for the first 6 months of follow-up even at late diagnosis age. Although combined analysis of SNP-based genotyping and WES is a powerful tool to reveal the genetic components of heterogeneous diseases, reanalysis of genome data still should be considered in unsolved patients. Also, biochemical screening helps us to decipher undiagnosed NDD that may be a treatable neurometabolic condition.
(© 2023. Fondazione Società Italiana di Neurologia.)
Databáze: MEDLINE
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