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 

Supplementary material

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Figure S1

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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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