A Novel Frameshift Variant in SON Causes Zhu-Tokita-Takenouchi-Kim Syndrome

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2020 Apr 16

PMID 32291808

Citations 11

Authors

Ya Tan

Ling Duan

Kai Yang

Qian Liu

Jing Wang

Zhe Dong

Zhi Li

Yiwen He

Yousheng Yan

Li Lin

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A mouse model of Zhu-Tokita-Takenouchi-Kim syndrome reveals indispensable SON functions in organ development and hematopoiesis.

Vukadin L, Park B, Mohamed M, Li H, Elkholy A, Torrelli-Diljohn A JCI Insight. 2024; 9(5).

PMID: 38290089 PMC: 10972584. DOI: 10.1172/jci.insight.175053.

A mouse model of ZTTK syndrome reveals indispensable SON functions in organ development and hematopoiesis.

Vukadin L, Park B, Mohamed M, Li H, Elkholy A, Torrelli-Diljohn A bioRxiv. 2023; .

PMID: 38014320 PMC: 10680872. DOI: 10.1101/2023.11.19.567732.

Expanding the mutational spectrum of ZTTK syndrome: A de novo variant with global developmental delay and malnutrition in a Chinese patient.

Tang S, You J, Liu L, OuYang H, Jiang N, Duan J Mol Genet Genomic Med. 2023; 11(8):e2188.

PMID: 37488749 PMC: 10422072. DOI: 10.1002/mgg3.2188.

Case report: A novel SON mutation in a Colombian patient with ZTTK syndrome.

Vasquez-Forero D, Masotto B, Ferrer-Avargues R, Moya C, Pachajoa H Front Genet. 2023; 14:1183362.

PMID: 37476413 PMC: 10354630. DOI: 10.3389/fgene.2023.1183362.

The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of Gene Focusing on Liver Involvement: Patient Report and Literature Review.

Pietrobattista A, Della Volpe L, Francalanci P, Talamanca L, Monti L, Lepri F Genes (Basel). 2023; 14(3).

PMID: 36981010 PMC: 10048019. DOI: 10.3390/genes14030739.

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