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 language | English (US) |
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Article number | 28 |
Journal | Human Genomics |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - Mar 4 2017 |
Keywords
- Angelman
- Dysmorphism
- Hypogonadism
- Mitochondrial
- Syndromic
- Vitamin D deficiency
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Drug Discovery