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

Handle URI:
http://hdl.handle.net/10754/626203
Title:
Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism
Authors:
Alsemari, Abdulaziz; Al-Younes, Banan; Goljan, Ewa; Jaroudi, Dyala; BinHumaid, Faisal; Meyer, Brian F.; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Monies, Dorota
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
Citation:
Alsemari 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.
Publisher:
Springer Nature
Journal:
Human Genomics
Issue Date:
14-Nov-2017
DOI:
10.1186/s40246-017-0124-4
Type:
Article
ISSN:
1479-7364
Sponsors:
This 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).
Additional Links:
http://link.springer.com/article/10.1186/s40246-017-0124-4
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorAlsemari, Abdulazizen
dc.contributor.authorAl-Younes, Bananen
dc.contributor.authorGoljan, Ewaen
dc.contributor.authorJaroudi, Dyalaen
dc.contributor.authorBinHumaid, Faisalen
dc.contributor.authorMeyer, Brian F.en
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorMonies, Dorotaen
dc.date.accessioned2017-11-23T11:51:29Z-
dc.date.available2017-11-23T11:51:29Z-
dc.date.issued2017-11-14en
dc.identifier.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.en
dc.identifier.issn1479-7364en
dc.identifier.doi10.1186/s40246-017-0124-4en
dc.identifier.urihttp://hdl.handle.net/10754/626203-
dc.description.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.en
dc.description.sponsorshipThis 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).en
dc.publisherSpringer Natureen
dc.relation.urlhttp://link.springer.com/article/10.1186/s40246-017-0124-4en
dc.rightsThis 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.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMitochondrialen
dc.subjectHypogonadismen
dc.subjectVitamin D deficiencyen
dc.subjectDysmorphismen
dc.subjectSyndromicen
dc.subjectAngelmanen
dc.titleRecessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadismen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalHuman Genomicsen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionSaudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.en
kaust.authorArold, Stefan T.en
All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.