# Case report: A novel TLK2 variant with a neuropsychiatric phenotype from a Chinese family

## TL;DR

A new TLK2 gene variant was found in a Chinese family, causing a neuropsychiatric disorder with symptoms like mood instability and developmental delays.

## Contribution

The study reports a novel TLK2 gene variant and expands the known phenotype of TLK2-related neurodevelopmental disorder.

## Key findings

- A novel heterozygous TLK2 gene variant (c.49dupG, p.E17Gfs*10) was identified in a Chinese family.
- The proband exhibited global developmental delay, autism-like symptoms, and elevated urine metabolite levels.
- The father of the proband carried the same variant and showed anxiety and irritability.

## Abstract

Tousled-like kinase 2 (TLK2) gene variant-related neurodevelopmental disorder was recently described. The haploinsufficiency of TLK2 was considered the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. So far, only four studies, conducted on 49 patients from North America and Europe, have been reported.

In this study, we reported a Chinese family with a TLK2-related neuropsychiatric phenotype. The proband, a boy aged 2 years and 6 months, presented with temper tantrums, mood lability, aggressiveness, congenital astigmatism, and distinctive facial dysmorphism. Whole-exome sequencing identified a novel heterozygous variation in TLK2 gene (c.49dupG, p. E17Gfs*10) in them. His father carried the same TLK2 gene variant and exhibited anxiety and irritability. The parental grandparents and other family members had no such variation. Moreover, the proband was found to have global developmental delay, autism-like symptoms, and mild elevated homo-vanillic acid (HVA) and 2,3-dihydroxy-2-methylbutyric acid levels tested in urine.

Herein, we identified a novel TLK2 variant from a Chinese family and reported a new neuropsychiatric phenotype. This study also expanded the genotype profile of the newly defined TLK2-related neurodevelopmental disorder.