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A Novel X-Linked Variant of IQSEC2 is Associated with Lennox–Gastaut Syndrome and Mild Intellectual Disability in Three Generations of a Korean Family
- Source :
- Genetic Testing and Molecular Biomarkers. 24:54-58
- Publication Year :
- 2020
- Publisher :
- Mary Ann Liebert Inc, 2020.
-
Abstract
- Aim: Lennox-Gastaut syndrome (LGS) is a severe type of childhood-onset epilepsy with multiple types of seizures, specific discharges on electroencephalography, and intellectual disability. However, LGS-related genes are largely unknown. To identify causative genes related to LGS, we collected and analyzed data from a three-generation Korean family in which one member had LGS and two had intellectual disability. Methods: Genomic DNAs were extracted from blood samples of all participants and used in whole-exome sequencing (WES). Genetic variants were detected by the Genome Analysis Toolkit and confirmed by Sanger sequencing. Variant pathogenicity was evaluated by prediction programs and the American College of Medical Genetics criteria. The LGS patient had generalized slow spike-and-wave discharges, multiple types of seizures, and developmental delay. Results: Analyses of the WES data from the family revealed a novel variant (c.1048G>A, p.Ala350Thr) in the IQ motif and Sec7 domain 2 (IQSEC2). This variant is within a highly evolutionarily conserved IQ-like motif, indicating a decrease in the calmodulin-binding capacity or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid transmission. The hemizygous variant in the male with LGS was a maternally inherited X-linked variant from the heterozygous maternal grandmother and mother, both of whom had intellectual disability. Conclusion: These findings indicate that the variant of IQSEC2 triggered both LGS and intellectual disability dependent on sex in this family. We report a novel X-linked inherited IQSEC2 variant for LGS and intellectual disability, which enhances the spectrum of variants in the IQ-like motif of IQSEC2.
- Subjects :
- 0301 basic medicine
Genetics
Sanger sequencing
medicine.medical_specialty
General Medicine
Biology
medicine.disease
Genome
03 medical and health sciences
symbols.namesake
Epilepsy
030104 developmental biology
0302 clinical medicine
030220 oncology & carcinogenesis
Intellectual disability
medicine
symbols
Medical genetics
Gene
Genetics (clinical)
Exome sequencing
Lennox–Gastaut syndrome
Subjects
Details
- ISSN :
- 19450257 and 19450265
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Genetic Testing and Molecular Biomarkers
- Accession number :
- edsair.doi...........c3ee61c2f6a9794f8b329afae7f0158a
- Full Text :
- https://doi.org/10.1089/gtmb.2019.0177