Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism
Meyer, Brian F.
Arold, Stefan T.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Online Publication Date2017-11-14
Print Publication Date2017-12
Permanent link to this recordhttp://hdl.handle.net/10754/626203
MetadataShow full item record
AbstractMost 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.
CitationAlsemari A, Al-Younes B, Goljan E, Jaroudi D, BinHumaid F, et al. (2017) Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism. Human Genomics 11. Available: http://dx.doi.org/10.1186/s40246-017-0124-4.
SponsorsThis work was funded through grants from King Faisal Specialist Hospital and Research Centre (RAC 2140029) and King Abdulaziz City for Science and Technology (KACST#13-MED2056-20).
Except where otherwise noted, this item's license is described as This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Neonatal encephalocardiomyopathy caused by mutations in VARS2.
- Authors: Baertling F, Alhaddad B, Seibt A, Budaeus S, Meitinger T, Strom TM, Mayatepek E, Schaper J, Prokisch H, Haack TB, Distelmaier F
- Issue date: 2017 Feb
- VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies.
- Authors: Diodato D, Melchionda L, Haack TB, Dallabona C, Baruffini E, Donnini C, Granata T, Ragona F, Balestri P, Margollicci M, Lamantea E, Nasca A, Powell CA, Minczuk M, Strom TM, Meitinger T, Prokisch H, Lamperti C, Zeviani M, Ghezzi D
- Issue date: 2014 Aug
- A novel compound heterozygous mutation in VARS2 in a newborn with mitochondrial cardiomyopathy: a case report of a Chinese family.
- Authors: Ma K, Xie M, He X, Liu G, Lu X, Peng Q, Zhong B, Li N
- Issue date: 2018 Nov 20
- Two novel EIF2S3 mutations associated with syndromic intellectual disability with severe microcephaly, growth retardation, and epilepsy.
- Authors: Moortgat S, Désir J, Benoit V, Boulanger S, Pendeville H, Nassogne MC, Lederer D, Maystadt I
- Issue date: 2016 Nov
- VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype.
- Authors: Begliuomini C, Magli G, Di Rocco M, Santorelli FM, Cassandrini D, Nesti C, Deodato F, Diodato D, Casellato S, Simula DM, Dessì V, Eusebi A, Carta A, Sotgiu S
- Issue date: 2019 May 7