Title |
Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism
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Published in |
Human Genomics, November 2017
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DOI | 10.1186/s40246-017-0124-4 |
Pubmed ID | |
Authors |
Abdulaziz Alsemari, Banan Al-Younes, Ewa Goljan, Dyala Jaroudi, Faisal BinHumaid, Brian F. Meyer, Stefan T. Arold, Dorota Monies |
Abstract |
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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Australia | 2 | 40% |
Spain | 1 | 20% |
Switzerland | 1 | 20% |
Unknown | 1 | 20% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 5 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 30 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 5 | 17% |
Other | 4 | 13% |
Student > Bachelor | 4 | 13% |
Researcher | 4 | 13% |
Student > Ph. D. Student | 2 | 7% |
Other | 4 | 13% |
Unknown | 7 | 23% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 9 | 30% |
Agricultural and Biological Sciences | 2 | 7% |
Nursing and Health Professions | 2 | 7% |
Biochemistry, Genetics and Molecular Biology | 2 | 7% |
Psychology | 2 | 7% |
Other | 5 | 17% |
Unknown | 8 | 27% |