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A Novel Homozygous YARS2 Mutation in Two Italian Siblings and a Review of Literature

  • Anna Ardissone
  • Eleonora LamanteaEmail author
  • Jade Quartararo
  • Cristina Dallabona
  • Franco Carrara
  • Isabella Moroni
  • Claudia Donnini
  • Barbara Garavaglia
  • Massimo Zeviani
  • Graziella Uziel
Case Report
Part of the JIMD Reports book series (JIMD, volume 20)

Abstract

YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase that catalyzes the covalent binding of tyrosine to its cognate mt-tRNA. Mutations in YARS2 have been identified in patients with myopathy, lactic acidosis, and sideroblastic anemia type 2 (MLASA2). We report here on two siblings with a novel mutation and a review of literature. The older patient presented at 2 months with marked anemia and lactic acidemia. He required periodic blood transfusions until 14 months of age. Cognitive and motor development was normal. His younger sister was diagnosed at birth, presenting with anemia and lactic acidosis at 1 month of age requiring periodical transfusions. She is now 14 months old and doing well. For both our patients, there was no clinical evidence of muscle involvement. We found a new homozygous mutation in YARS2, located in the α-anticodon-binding (αACB) domain, involved in the interaction with the anticodon of the cognate mt-tRNATyr.

Our study confirms that MLASA must be considered in patients with congenital sideroblastic anemia and underlines the importance of early diagnosis and supportive therapy in order to prevent severe complications. Clinical severity is variable among YARS2-reported patients: our review of the literature suggests a possible phenotype-genotype correlation, although this should be confirmed in a larger population.

Keywords

Mitochondria Myopathy, lactic acidosis, and sideroblastic anemia Tyrosyl-tRNA synthetase YARS2 

Notes

Acknowledgments

This work was supported by Fondazione Pierfranco e Luisa Mariani (CM23), Fondazione Telethon (grant GGP11011), Cell line and DNA Bank of Genetic Movement Disorders and Mitochondrial Disesases of Telethon Network of Genetics Biobanks (grant GTB12001) and the Italian Association of Mitochondrial Disease Patients and Families (Mitocon ONLUS).

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Anna Ardissone
    • 1
  • Eleonora Lamantea
    • 2
    Email author
  • Jade Quartararo
    • 3
  • Cristina Dallabona
    • 3
  • Franco Carrara
    • 2
  • Isabella Moroni
    • 1
  • Claudia Donnini
    • 3
  • Barbara Garavaglia
    • 2
  • Massimo Zeviani
    • 2
    • 4
  • Graziella Uziel
    • 1
  1. 1.Unit of Child Neurology, Foundation IRCCS Neurological Institute “Carlo Besta”MilanItaly
  2. 2.Unit of Molecular Neurogenetics – Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute “Carlo Besta”MilanItaly
  3. 3.Department of Life SciencesUniversity of ParmaParmaItaly
  4. 4.MRC Mitochondrial Biology UnitCambridgeUK

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