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neurogenetics

, Volume 16, Issue 2, pp 145–149 | Cite as

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

  • Ramona Salvarinova
  • Cynthia X. Ye
  • Andrea Rossi
  • Roberta Biancheri
  • Elke H. Roland
  • Paul Pavlidis
  • Colin J. Ross
  • Maja Tarailo-Graovac
  • Wyeth W. Wasserman
  • Clara D. M. van Karnebeek
Short Communication

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.

Keywords

Epilepsy Microcephaly Developmental delay Hypomyelination Cerebral atrophy Genomics 

Notes

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)

Supplementary material

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Figure S1

(JPEG 1736 kb)

10048_2014_432_MOESM1_ESM.docx (18 kb)
ESM 1 (DOCX 18 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ramona Salvarinova
    • 1
    • 2
    • 6
  • Cynthia X. Ye
    • 2
    • 4
    • 5
    • 6
  • Andrea Rossi
    • 7
  • Roberta Biancheri
    • 8
  • Elke H. Roland
    • 3
    • 6
  • Paul Pavlidis
    • 6
  • Colin J. Ross
    • 2
    • 4
    • 5
    • 6
  • Maja Tarailo-Graovac
    • 2
    • 4
    • 5
    • 6
  • Wyeth W. Wasserman
    • 2
    • 4
    • 5
    • 6
  • Clara D. M. van Karnebeek
    • 1
    • 2
    • 4
    • 6
  1. 1.Division of Biochemical Diseases, Rm K3-201, Department of PediatricsB.C. Children’s & Women’s HospitalVancouverCanada
  2. 2.Treatable Intellectual Disability Endeavour in British ColumbiaB.C. Children’s & Women’s HospitalVancouverCanada
  3. 3.Division of Pediatric Neurology, Department of PediatricsB.C. Children’s & Women’s HospitalVancouverCanada
  4. 4.Center for Molecular Medicine and TherapeuticsChild and Family Research InstituteVancouverCanada
  5. 5.Department of Medical GeneticsBC Women’s Hospital & Health CentreVancouverUSA
  6. 6.University of British ColumbiaVancouverCanada
  7. 7.Department of NeuroradiologyIstituto Giannina GasliniGenoaItaly
  8. 8.Department of Child NeuropsychiatryIstituto Giannina GasliniGenoaItaly

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