Identification of a novel nonsense IQSEC2 variant in a child with X-linked intellectual disability.
10.3760/cma.j.issn.1003-9406.2020.08.005
- Author:
Ruohao WU
1
;
Wenting TANG
;
Kunyin QIU
;
Danxia TANG
;
Xiaojuan LI
;
Xiangyang LUO
Author Information
1. Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. luoxy33@126.com.
- Publication Type:Journal Article
- From:
Chinese Journal of Medical Genetics
2020;37(8):823-827
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for a child featuring X-linked intellectual disability.
METHODS:The 1-year-and-6-month-old child presented with growth retardation, intellectual disability and bilateral alternating squint. With DNA extracted from the child and his parents' peripheral venous blood samples, whole exome sequencing was carried out to identify potential variants that can explain his condition. Suspected variants were validated by Sanger sequencing. The impact of variants was predicted by bioinformatic tools.
RESULTS:The child was found to harbor a de novo nonsense c.3163C>T (p.Arg1055*) variant of the IQSEC2 gene. The variant, unreported previously, was predicted to be pathogenic based on MutationTaster, PROVEAN and SIFT. Analysis using a HomoloGene system suggested Arg1055 in IQSEC2 residues to be highly conserved evolutionarily, and that replacement of Arg1055 may cause destroy of the PH domain (AA 951-1085) and serious damage to the function of IQSEC2 protein. Analysis with UCSF chimera software suggested that the c.3163C>T (p.Arg1055*) variant can induce serious damages to the secondary structures of IQSEC2 protein, causing loss of its function.
CONCLUSION:The patient's condition may be attributed to the de novo nonsense variant c.3163C>T (p.Arg1055*) of the IQSEC2 gene.
