Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism.
Hum Genomics
; 11(1): 28, 2017 Nov 14.
Article
em En
| MEDLINE
| ID: mdl-29137650
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Valina-tRNA Ligase
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Hormônio do Crescimento Humano
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Epilepsia
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Antígenos HLA
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Hipogonadismo
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Deficiência Intelectual
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
Hum Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Arábia Saudita