Skip to main content

Advertisement

SpringerLink
Log in

Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities

  • Short Communication
  • Published:
neurogenetics Aims and scope Submit manuscript

Abstract

We describe a family with QARS deficiency due to compound heterozygous QARS mutations, including c.1387G > A (p.R463*) in the catalytic core domain and c.2226C > G (p.Q742H) in the anticodon domain, both previously unreported and predicted damaging. The phenotype of the male index further confirms this specific aminoacyl-transfer RNA (tRNA) synthetase disorder as a novel genetic cause of progressive microcephaly with diffuse cerebral atrophy, severely deficient myelination, intractable seizures, and developmental arrest. However, in contrast to the two hitherto published families, the cerebellum and its myelination are not affected. An awareness that QARS mutations may cause isolated supratentorial changes is crucial for properly directing genetic analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Zhang X, Ling J, Barcia G, Jing L, Wu J, Barry BJ, Mochida GH, Hill RS, Weimer JM, Stein Q et al (2014) Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. Am J Hum Genet 94:547–558

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. van Karnebeek CDM, Shevell MI, Zschocke J, Moeschler J, Stockler S (2014) The metabolic evaluation of the child with an intellectual developmental disorder: diagnostic algorithm for identification of treatable causes and new digital resource. Mol Genet Metab 111:428–438

    Article  PubMed  Google Scholar 

  3. Perona JJ (2000) Glutaminyl-tRNA Synthetases. In: Madam Curie Science Database. Austin (TX): Landes Bioscience; (http://www.ncbi.nlm.nih.gov/books/NBK6506/)

  4. Antonellis A, Green ED (2008) The role of aminoacyl-tRNA synthetases in genetic diseases. Annu Rev Genomics Hum Genet 9:87–107

    Article  CAS  PubMed  Google Scholar 

  5. Yao P, Fox PL (2013) Aminoacyl-tRNA synthetases in medicine and disease. EMBO Mol Med 5:332–343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Cader MZ, Ren J, James PA et al (2007) Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy. FEBS Lett 581:2959–2964

    Article  CAS  PubMed  Google Scholar 

  7. Nangle LA, Zhang W, Xie W et al (2007) Charcot-Marie-Tooth disease-associated mutant tRNA synthetases linked to altered dimer interface and neurite distribution defect. Proc Natl Acad Sci U S A 104:11239–11244

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Eskuri JM, Stanley CM, Moore SA, Mathews KD (2012) Infantile onset CMT2D/dSMA V in monozygotic twins due to a mutation in the anticodon-binding domain of GARS. J Peripher Nerv Syst JPNS 17:132–134

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the family for their participation in this study; Dr. M. van der Knaap (Free University Medical Centre, Amsterdam NL) for neuroradiologic evaluation; Dr. R. Burgess (Jackson Laboratory, Maine U.S.A.), Dr. P. Tan and Dr. L. French for expert input regarding candidate genes; Dr. R. Buck for clinical management of the patient; Dr. M. Aroichaine, Dr. J. Gardiner, Dr. C. Lyons, Dr. A. Merkur for ophthalmological evaluation; Mrs. X. Han for Sanger sequencing; Mr. B. Sayson for consenting and data management; Mrs. M. Higginson for DNA extraction, sample handling, and technical data (University of British Columbia, Vancouver, CA).

Ethical standards

The authors declare that the experiments comply with the current laws of Canada, the country in which they were performed.

Funding

This work was supported by funding from the B.C. Children’s Hospital Foundation as “1st Collaborative Area of Innovation” (www.tidebc.org), Genome BC (SOF-195 grant), the Canadian Institutes of Health Research (#301221 grant), and the British Columbia Clinical Genomics Network [grant number BCCGN00031]. Informatics infrastructure was supported by Genome BC and Genome Canada (ABC4DE Project). CvK is a Michael Smith Foundation for Health Research Scholar.

Conflict of interest

The authors declare that they have no conflict(s) of interest.

Web resources

NHLBI ESP (http://evs.gs.washington.edu/EVS/)

Online Mendelian Inheritance in Man (http://www.omim.org)

TIDE-BC (http://www.tidebc.org)

Author information

Authors and Affiliations

  1. Division of Biochemical Diseases, Rm K3-201, Department of Pediatrics, B.C. Children’s & Women’s Hospital, 4480 Oak Street, Vancouver, BC, V6H 3 V4, Canada

    Ramona Salvarinova & Clara D. M. van Karnebeek

  2. Treatable Intellectual Disability Endeavour in British Columbia, B.C. Children’s & Women’s Hospital, 4480 Oak Street, Vancouver, BC, V6H 3 V4, Canada

    Ramona Salvarinova, Cynthia X. Ye, Colin J. Ross, Maja Tarailo-Graovac, Wyeth W. Wasserman & Clara D. M. van Karnebeek

  3. Division of Pediatric Neurology, Department of Pediatrics, B.C. Children’s & Women’s Hospital, 4480 Oak Street, Vancouver, BC, V6H 3 V4, Canada

    Elke H. Roland

  4. Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, 950 28th Ave W, Vancouver, BC, V5Z 4H4, Canada

    Cynthia X. Ye, Colin J. Ross, Maja Tarailo-Graovac, Wyeth W. Wasserman & Clara D. M. van Karnebeek

  5. Department of Medical Genetics, BC Women’s Hospital & Health Centre, 4500 Oak Street, Room C234, Vancouver, BC, V6H 3N1, USA

    Cynthia X. Ye, Colin J. Ross, Maja Tarailo-Graovac & Wyeth W. Wasserman

  6. University of British Columbia, Vancouver, BC, Canada

    Ramona Salvarinova, Cynthia X. Ye, Elke H. Roland, Paul Pavlidis, Colin J. Ross, Maja Tarailo-Graovac, Wyeth W. Wasserman & Clara D. M. van Karnebeek

  7. Department of Neuroradiology, Istituto Giannina Gaslini, Via G. Gaslini 5, 16147, Genoa, Italy

    Andrea Rossi

  8. Department of Child Neuropsychiatry, Istituto Giannina Gaslini, Via G. Gaslini 5, 16147, Genoa, Italy

    Roberta Biancheri

Authors
  1. Ramona Salvarinova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cynthia X. Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberta Biancheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elke H. Roland
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul Pavlidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Colin J. Ross
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maja Tarailo-Graovac
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wyeth W. Wasserman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Clara D. M. van Karnebeek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clara D. M. van Karnebeek.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Figure S1

(JPEG 1736 kb)

ESM 1

(DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salvarinova, R., Ye, C.X., Rossi, A. et al. Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities. Neurogenetics 16, 145–149 (2015). https://doi.org/10.1007/s10048-014-0432-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10048-014-0432-y

Keywords

Search

Navigation