Paternal uniparental disomy of chromosome 16 resulting in homozygosity of a GPT2 mutation causes intellectual and developmental disability

Jing Liu; Baiyun Chen; Yuchun Liu; Jinghui Kong; Bo Zhang; Liang Han; Daoqi Mei; Cai Yun Ma; Qing Shang; Zhenhua Xie; Mengjun Xiao; Shiyue Mei; Yaodong Zhang; Chao Gao; Dongxiao Li

doi:10.1016/j.ejmg.2022.104554

Paternal uniparental disomy of chromosome 16 resulting in homozygosity of a GPT2 mutation causes intellectual and developmental disability

Eur J Med Genet. 2022 Sep;65(9):104554. doi: 10.1016/j.ejmg.2022.104554. Epub 2022 Jul 3.

Authors

Jing Liu¹, Baiyun Chen², Yuchun Liu³, Jinghui Kong³, Bo Zhang³, Liang Han⁴, Daoqi Mei⁵, Cai Yun Ma⁴, Qing Shang⁴, Zhenhua Xie³, Mengjun Xiao³, Shiyue Mei³, Yaodong Zhang³, Chao Gao⁶, Dongxiao Li⁷

Affiliations

¹ Henan Neurodevelopment Engineering Research Center for Children, Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China. Electronic address: [email protected].
² Department of Pediatric Rehabilitation Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China. Electronic address: [email protected].
³ Henan Neurodevelopment Engineering Research Center for Children, Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China.
⁴ Department of Pediatric Rehabilitation Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China.
⁵ Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China. Electronic address: [email protected].
⁶ Department of Pediatric Rehabilitation Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China. Electronic address: [email protected].
⁷ Henan Neurodevelopment Engineering Research Center for Children, Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China. Electronic address: [email protected].

PMID: 35793769
DOI: 10.1016/j.ejmg.2022.104554

Abstract

Recessive mutations in glutamate pyruvate transaminase 2 (GPT2) have recently been found to be associated with intellectual and developmental disability (IDD). In this study, we discovered a homozygous missense variant, NM_133443: [c.1172C > T, p. Pro391Leu], of GPT2 on chromosome 16 in a proband diagnosed with IDD through trio whole-exome sequencing (WES). The pathogenicity of the variant was further verified by bioinformatics analysis and functional studies in vitro. This autosomal recessive disease was caused by paternal uniparental disomy (UPD) which was further proven by single nucleotide polymorphism array (SNP array). In past literature, recessive diseases in chromosome 16 were usually due to maternal UPD where Mendel's law of inheritance was not applicable. However, in our case we found that paternal UPD can cause recessive diseases related to the GPT2 gene on chromosome 16. Our study provides an important line of evidence for the diagnosis of GPT2-related intellectual developmental disorders.

Keywords: GPT2; Intellectual and developmental disability; Paternal uniparental disomy; Single nucleotide polymorphism array.

Publication types

Case Reports

MeSH terms

Chromosomes, Human, Pair 16 / genetics
Developmental Disabilities / genetics
Homozygote
Humans
Intellectual Disability* / genetics
Transaminases / genetics
Uniparental Disomy* / genetics

Substances

GPT2 protein, human
Transaminases