Open AccessA novel frameshift variant in SON causes Zhu‐Tokita‐Takenouchi‐Kim Syndrome
Author(s) -
Tan Ya,
Duan Ling,
Yang Kai,
Liu Qian,
Wang Jing,
Dong Zhe,
Li Zhi,
He Yiwen,
Yan Yousheng,
Lin Li
Publication year - 2020
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23326
Subject(s) - frameshift mutation , proband , sanger sequencing , exome sequencing , intellectual disability , genetics , global developmental delay , medicine , biology , gene , exon , mutation , phenotype
Background Zhu‐Tokita‐Takenouchi‐Kim syndrome is a severe multisystem developmental disorder characterized by intellectual disability, developmental delay, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. This syndrome is caused by heterozygous pathogenic variants in the SON gene at chromosome 21q22.1. Objectives The aim of this study was to investigate the pathogenesis of a 4‐year‐old Chinese child who displayed severe intellectual disability, delayed psychomotor development, and facial dysmorphism. Methods A sequential detection including chromosome karyotyping, chromosome microarray analysis (CMA), and whole‐exome sequencing (WES) was performed on this child. The familial verification of WES result was conducted by Sanger sequencing. Results A de novo frameshift variant SON : c.5230delC (p.Arg1744ValfsTer29) was identified in the proband. The identical variant was not found in his family members. The frequencies of this variant in gnomAD/gnomAD_EAS databases were both none. Conclusions This study substantiates that SON : c.5230delC (p.Arg1744ValfsTer29) is a pathogenic variant of Zhu‐Tokita‐Takenouchi‐Kim syndrome and it is the first time to report Zhu‐Tokita‐Takenouchi‐Kim syndrome in China.