Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism

Abdulaziz Alsemari, Banan Al-Younes, Ewa Goljan, Dyala Jaroudi, Faisal Binhumaid, Brian F. Meyer, Stefan T. Arold, Dorota Monies*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: Most mitochondrial and cytoplasmic aminoacyl-tRNA synthetases (aaRSs) are encoded by nuclear genes. Syndromic disorders resulting from mutation of aaRSs genes display significant phenotypic heterogeneity. We expand aaRSs-related phenotypes through characterization of the clinical and molecular basis of a novel autosomal-recessive syndrome manifesting severe mental retardation, ataxia, speech impairment, epilepsy, short stature, microcephaly, hypogonadism, and growth hormone deficiency. Results: A G>A variant in exon 29 of VARS2 (c.3650G>A) (NM-006295) was identified in the index case. This homozygous variant was confirmed by Sanger sequencing and segregated with disease in the family studied. The c.3650G>A change results in alteration of arginine to histidine at residue 1217 (R1217H) of the mature protein and is predicted to be pathogenic. Conclusions: These findings contribute to a growing list of aaRSs disorders, broadens the spectrum of phenotypes attributable to VARS2 mutations, and provides new insight into genotype-phenotype correlations among the mitochondrial synthetase genes.

Original languageEnglish (US)
Article number28
JournalHuman Genomics
Volume11
Issue number1
DOIs
StatePublished - Mar 4 2017

Keywords

  • Angelman
  • Dysmorphism
  • Hypogonadism
  • Mitochondrial
  • Syndromic
  • Vitamin D deficiency

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

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