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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

Authors :
Soo Young Jun
Min Hyuk Choi
Su Jin Jeon
Joon Won Kang
Ju-Sik Min
Iksu Byeon
Jeong Ju Lee
Nam-Soon Kim
Ji Yong Yoon
Jin Ok Yang
Yong Jae Lee
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.

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