Novel familial IQSEC2 pathogenic sequence variant associated with neurodevelopmental disorders and epilepsy
| Autor: | Marcela Vilémová, Jan Oppelt, Vladimíra Vallová, Hana Polackova, Michal Ryzí, Petr Kuglík, Lenka Krskova, Eva Hladílková, Renata Gaillyová, Marketa Wayhelova |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proband Male Biology Frameshift mutation 03 medical and health sciences Cellular and Molecular Neuroscience Epilepsy symbols.namesake 0302 clinical medicine X Chromosome Inactivation Genetics medicine Guanine Nucleotide Exchange Factors Humans Child Frameshift Mutation Gene Skewed X-inactivation Genetics (clinical) Oligonucleotide Array Sequence Analysis Sanger sequencing Comparative Genomic Hybridization Genetic Variation High-Throughput Nucleotide Sequencing medicine.disease Molecular diagnostics Chromosome Banding 030104 developmental biology Phenotype Neurodevelopmental Disorders Child Preschool Karyotyping symbols Autism Female 030217 neurology & neurosurgery Algorithms Gene Deletion |
| Zdroj: | Neurogenetics. 21(4) |
| ISSN: | 1364-6753 0011-1112 |
| Popis: | Pathogenic sequence variants in the IQ motif– and Sec7 domain–containing protein 2 (IQSEC2) gene have been confirmed as causative in the aetiopathogenesis of neurodevelopmental disorders (intellectual disability, autism) and epilepsy. We report on a case of a family with three sons; two of them manifest delayed psychomotor development and epilepsy. Initially proband A was examined using a multistep molecular diagnostics algorithm, including karyotype and array-comparative genomic hybridization analysis, both with negative results. Therefore, probands A and B and their unaffected parents were enrolled for an analysis using targeted “next-generation” sequencing (NGS) with a gene panel ClearSeq Inherited DiseaseXT (Agilent Technologies) and verification analysis by Sanger sequencing. A novel frameshift variant in the X-linked IQSEC2 gene NM_001111125.2:c.1813_1814del, p.(Asp605Profs*3) on protein level, was identified in both affected probands and their asymptomatic mother, having skewed X chromosome inactivation (XCI) (100:0). As the IQSEC2 gene is a known gene escaping from XCI in humans, we expect the existence of mechanisms maintaining the normal or enough level of the IQSEC2 protein in the asymptomatic mother. Further analyses may help to the characterization of the presented novel frameshift variant in the IQSEC2 gene as well as to elucidate the mechanisms leading to the rare asymptomatic phenotypes in females. |
| Databáze: | OpenAIRE |
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