Novel GLDC variants causing nonketotic hyperglycinemia in Chinese patients
Author:
Zhao Xiangyue1ORCID, Zhang Guoqing2, Dong Shumei2, Yao Ru-En1, Li Niu1, Yu Tingting1, Bei Fei2, Wang Jian1
Affiliation:
1. Department of Medical Genetics and Molecular Diagnostic Laboratory , Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine , Shanghai , P.R. China 2. Department of Neonatal Intensive Care Unit (NICU) , Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine , Shanghai , P.R. China
Abstract
Abstract
Objectives
Glycine decarboxylase gene (GLDC) mutations cause nonketotic hyperglycinemia (NKH). Patients of NKH usually have heterogeneous phenotypes including respiratory failure, lethargy, myoclonic jerks, and hypotonia. The excessive glycine accumulation in brain is a crucial pathogenic mechanism.
Methods
We performed a clinical phenotypic analysis of two Chinese patients and conducted whole exome sequencing to detect possible pathogenic genes. Transcriptional experiments were carried out to evaluate the impact of GLDC c.862-2A>G on GLDC transcript splicing.
Results
GLDC variants were identified in both patients who mainly presented with hypotonia, apnea, and lethargy patient 1 had compound heterozygous variants, which were c.334+5G>C and c.862-2A>G, while patient 2 had c.862-2A>G and c.2098C>G (p.P700A) in GLDC. Transcriptional experiments of GLDC c.862-2A>G revealed the presence of aberrant transcripts leading to truncated protein products.
Conclusions
Both patients were diagnosed with neonatal NKH. Two novel splice-site variations in GLDC, c.334+5G>C and c.862-2A>G, were identified. The c.862-2A>G variation was found in both patients and was confirmed to affect the splicing of GLDC. Our study enriched our knowledge of the genotypic and the phenotypic spectrum of NKH.
Funder
Program of Shanghai Academic/Technology Research Leader Clinical Research Plan of SHDC
Publisher
Walter de Gruyter GmbH
Subject
Biochemistry (medical),Clinical Biochemistry,Discrete Mathematics and Combinatorics
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