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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Medical Genetics 1/2018

A novel compound heterozygous variant identified in GLDC gene in a Chinese family with non-ketotic hyperglycinemia

Zeitschrift:
BMC Medical Genetics > Ausgabe 1/2018
Autoren:
Yiming Lin, Zhenzhu Zheng, Wenjia Sun, Qingliu Fu
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12881-017-0517-1) contains supplementary material, which is available to authorized users.

Abstract

Background

Non-ketotic hyperglycinemia (NKH) is a rare, devastating autosomal recessive disorder of glycine metabolism with a very poor prognosis. Currently, few studies have reported genetic profiling of Chinese NKH patients. This study aimed to identify the genetic mutations in a Chinese family with NKH.

Methods

A Chinese family of Han ethnicity, with three siblings with NKH was studied. Sanger sequencing and multiplex ligation-dependent probe amplification combined with SYBR green real-time quantitative PCR was used to identify potential mutations in the GLDC, AMT and GCSH genes. The potential pathogenicity of the identified missense mutation was analyzed using SIFT, PolyPhen-2, PROVEAN and MutationTaster software.

Results

All patients exhibited severe and progressive clinical symptoms, including lethargy, hypotonia and seizures, and had greatly elevated glycine levels in their plasma and CSF. Molecular genetic analysis identified compound heterozygous variants in the GLDC gene in these three siblings, including a novel missense variant c.2680A > G (p.Thr894Ala) in exon 23 and a heterozygous deletion of exon 3, which were inherited respectively from their parents. In silico analysis, using several different types of bioinformatic software, predicted that the novel variant c.2680A > G in the GLDC gene was pathogenic. Moreover, the deletion of exon 3 was identified for the first time in a Chinese population.

Conclusions

A novel missense variant and a previously reported deletion in GLDC gene were identified. The two variants of GLDC gene identified probably underlie the pathogenesis of non-ketotic hyperglycinemia in this family, and also enrich the mutational spectrum of GLDC gene.
Zusatzmaterial
Additional file 1: Table S1. List of the primers used for Sanger sequencing and Q-PCR (DOCX 13 kb)
12881_2017_517_MOESM1_ESM.docx
Additional file 2: Table S2. Pathogenicity prediction analysis of GLDC c.2680A > G alteration (DOC 29 kb)
12881_2017_517_MOESM2_ESM.doc
Additional file 3: Figure S1. The illustration of breakpoints in exon 3 deletion (TIFF 891 kb)
12881_2017_517_MOESM3_ESM.tif
Literatur
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