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BMC Med Genet. 2018 Nov 20;19(1):202. doi: 10.1186/s12881-018-0689-3.

A novel compound heterozygous mutation in VARS2 in a newborn with mitochondrial cardiomyopathy: a case report of a Chinese family.

Ma K1,2, Xie M1,2, He X1,2, Liu G1,2, Lu X2, Peng Q2, Zhong B3,4, Li N5,6.

Author information

1
Department of Neonatal Intensive Care Unit, Dongguan Children's Hospital, Dongguan, 523325, Guangdong, China.
2
Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, 523325, Guangdong, China.
3
Department of Neonatal Intensive Care Unit, Dongguan Children's Hospital, Dongguan, 523325, Guangdong, China. zbomao@163.com.
4
Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, 523325, Guangdong, China. zbomao@163.com.
5
Department of Neonatal Intensive Care Unit, Dongguan Children's Hospital, Dongguan, 523325, Guangdong, China. mean163@163.com.
6
Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, 523325, Guangdong, China. mean163@163.com.

Abstract

BACKGROUND:

Genetic defects in the mitochondrial aminoacyl-tRNA synthetase are important causes of mitochondrial disorders. VARS2 is one of the genes encoding aminoacyl-tRNA synthetases. Recently, an increasing number of pathogenic variants of VARS2 have been reported.

CASE PRESENTATION:

We report the novel compound heterozygous pathogenic VARS2 mutations c.643 C > T (p. His215Tyr) and c.1354 A > G (p. Met452Val) in a female infant who presented with poor sucking at birth, poor activity, hyporeflexia, hypertonia, persistent pulmonary hypertension of newborn (PPHN), metabolic acidosis, severe lactic acidosis, expansion and hypertrophic cardiomyopathy. These heterozygous mutations were carried individually by the proband's parents and elder sister; the two mutations segregated in the family and were the cause of the disease in the proband.The c.643 C > T (p. His215Tyr) mutation was not described in the ExaC, GNomAD and 1000 Genomes Project databases, and the frequency of c.1354 A > G (p. Met452Val) was < 0.001 in these gene databases.The two mutated amino acids were located in a highly conserved region of the VARS2 protein that is important for its interaction with the cognate tRNA. The two missense mutations were predicted by online tools to be damaging and deleterious.

CONCLUSIONS:

Our report expands the spectrum of known pathogenicVARS2 variants associated with mitochondrial disorders in humans.VARS2 deficiency may cause a severe neonatal presentation with structural cardiac abnormalities.

KEYWORDS:

Cardiomyopathy; Mitochondrial disorders; Neonate; VARS2

PMID:
30458719
PMCID:
PMC6247698
DOI:
10.1186/s12881-018-0689-3
[Indexed for MEDLINE]
Free PMC Article

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