Novel Mutations in the GTPBP3 Gene for Mitochondrial Disease and Characteristics of Related Phenotypic Spectrum: The First Three Cases From China

Authors

Hui-Ming Yan
Zhi-Mei Liu
Bei Cao
Victor Wei Zhang
Yi-Duo He
Zheng-Jun Jia
Hui Xi
Jing Liu
Fang Fang
Hua Wang

Publication Date

1-1-2021

Journal

Frontiers in Genetics

DOI

10.3389/fgene.2021.611226

PMID

34276756

PMCID

PMC8281222

PubMedCentral® Posted Date

7-1-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

mitochondrial disease, Combined Oxidative Phosphorylation Deficiency 23, GTPBP3 gene, hyperlactacidemia, hyperalaninemia

Abstract

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C > T (p. A138V) and c.509_510del (p. E170Gfs∗42) in GTPBP3. Patient 2 was a compound heterozygote with novel mutations c.544G > T (p. G182X) and c.785A > C (p.Q262P), while patient 3 was a compound heterozygote with a previously reported mutation c.424G > A (p.E142K) and novel mutation c.785A > C (p.Q262P). In conclusion, we first describe three Chinese individuals with COXPD23, and discuss the genotype-phenotype correlations of GTPBP3 mutations. Our findings provide novel information in the diagnosis and genetic counseling of patients with mitochondrial disease.

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