Advertisement

neurogenetics

, Volume 15, Issue 3, pp 157–159 | Cite as

AIMP1 deficiency presents as a cortical neurodegenerative disease with infantile onset

  • L. Armstrong
  • R. Biancheri
  • C. Shyr
  • A. Rossi
  • G. Sinclair
  • C. J. Ross
  • M. Tarailo-Graovac
  • W. W. Wasserman
  • C. D. M. van Karnebeek
Short Communication

Abstract

We report the second family with AIMP1 deficiency, due to a homozygous truncating AIMP1 (g.107248613 C > T) mutation. This female showed early-onset developmental arrest, intractable epileptic spasms, microcephaly, and a rapid clinical course leading to premature death, associated with cerebral atrophy and myelin deficiency on brain MRI. Clinical and neuroimaging findings are consistent with a primary neuronal degenerative disorder, rather than with the previously reported Perlizaeus-Merzbacher-like phenotype. Given its critical role in neurofilament assembly 16, impaired myelin formation is due to neuronal/axonal dysfunction. We propose that AIMP1 deficiency be added to the differential diagnosis of infantile onset, progressive neurodegenerative disease.

Keywords

Seizures Epilepsy Microcephaly Developmental delay Hypomyelination Cerebral atrophy Neuron Genomics 

Notes

Acknowledgments

We gratefully acknowledge the family for their participation in this study, Dr. K. Selby and Dr. L. Cline for the clinical management of the patient, Mrs. X. Han for the Sanger sequencing, Mr. B. Sayson for consenting and data management, and Mrs. M. Higginson for DNA extraction and sample handling. The authors have no conflict of interest to declare.

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), and the Canadian Institutes of Health Research (#301221 grant), BC Clinical Genomics Network (#00031 grant).

Conflict of interest

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

References

  1. 1.
    Feinstein M, Markus B, Noyman I, Shalev H, Flusser H, Shelef I, Liani-Leibson K, Shorer Z, Cohen I, Khateeb S, Sivan S, Birk OS (2010) Pelizaeus-Merzbacher-like disease caused by AIMP1/p43 homozygous mutation. Am J Hum Genet 87:820–828PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Biancheri R, Rossi E, Zara F, Filocamo M (2011) AIMP1/p43 mutation and PMLD. Am J Hum Genet 88:391PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Boespflug-Tanguy O, Aubourg P, Dorboz I, Bégou M, Giraud G, Sarret C, Vaurs-Barrière C (2011) Neurodegenerative disorder related to AIMP1/p43 mutation is not a PMLD. Am J Hum Genet 88:392–393PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    van Karnebeek CD, Shevell M, Zschocke J, Moeschler JB, 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 111:428–438PubMedCrossRefGoogle Scholar
  5. 5.
    Steenweg ME, Vanderver A, Blaser S, Bizzi A, de Koning TJ, Mancini GM, van Wieringen WN, Barkhof F, Wolf NI, van der Knaap MS (2010) Magnetic resonance imaging pattern recognition in hypomyelinating disorders. Brain 133:2971–2982PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Di Rocco M, Rossi A, Parenti G, Allegri AE, Filocamo M, Pessagno A, Tortori-Donati P, Minetti C, Biancheri R (2005) Different molecular mechanisms leading to white matter hypomyelination in infantile onset lysosomal disorders. Neuropediatrics 36:265–269PubMedCrossRefGoogle Scholar
  7. 7.
    Zhu X, Liu Y, Yin Y, Zhang B, Kim S, Zhou J (2009) MSC p43 required for axonal development in motor neurons. Proc Natl Acad Sci U S A 106:15944–15949PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • L. Armstrong
    • 2
    • 4
    • 5
  • R. Biancheri
    • 6
  • C. Shyr
    • 2
    • 3
    • 5
  • A. Rossi
    • 7
  • G. Sinclair
    • 2
    • 4
    • 5
  • C. J. Ross
    • 2
    • 3
    • 4
    • 5
  • M. Tarailo-Graovac
    • 2
    • 3
    • 5
  • W. W. Wasserman
    • 2
    • 3
    • 5
  • C. D. M. van Karnebeek
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Division of Biochemical Diseases, Department of PediatricsB.C. Children’s Hospital, Centre for Molecular Medicine & Therapeutic, University of British ColumbiaVancouverCanada
  2. 2.Treatable Intellectual Disability Endeavour in British ColumbiaVancouverCanada
  3. 3.Center for Molecular Medicine and Therapeutics; Child and Family Research InstituteVancouverCanada
  4. 4.B.C. Children’s and Women’s HospitalVancouverCanada
  5. 5.University of British ColumbiaVancouverCanada
  6. 6.Child Neurology and Psychiatry UnitIstituto G. GasliniGenoaItaly
  7. 7.Pediatric Neuroradiology UnitIstituto G. GasliniGenoaItaly

Personalised recommendations