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.
Department of Pediatric Rehabilitation Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China.
Eur J Med Genet. 2022 Sep;65(9):104554. doi: 10.1016/j.ejmg.2022.104554. Epub 2022 Jul 3.
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.
谷氨酸丙酮酸转氨酶 2（GPT2）的隐性突变最近被发现与智力和发育障碍（IDD）有关。在这项研究中，我们通过三人全外显子组测序（WES）发现了一个先证者染色体 16 上 GPT2 的纯合错义变异 NM_133443：[c.1172C>T，p.Pro391Leu]。通过生物信息学分析和体外功能研究进一步验证了该变异的致病性。这种常染色体隐性疾病是由父源单亲二体性（UPD）引起的，进一步通过单核苷酸多态性微阵列（SNP 微阵列）得到证实。在过去的文献中，染色体 16 上的隐性疾病通常是由于母源 UPD 引起的，孟德尔遗传定律不适用。然而，在我们的病例中，我们发现父源 UPD 可导致与染色体 16 上 GPT2 基因相关的隐性疾病。我们的研究为 GPT2 相关智力发育障碍的诊断提供了重要的证据。
