Abstract
Dysequilibrium syndrome (DES) is a non-progressive congenital ataxia characterized by severe intellectual deficit, truncal ataxia and markedly delayed, quadrupedal or absent ambulation. Recessive loss-of-function mutations in the very low density lipoprotein receptor (VLDLR) gene represent the most common cause of DES. Only two families have been reported harbouring homozygous missense mutations, both with a similarly severe phenotype. We report an Italian girl with very mild DES caused by the novel homozygous VLDLR missense mutation p.(C419Y). This unusually benign phenotype possibly relates to a less disruptive effect of the mutation, falling within a domain (EGF-B) not predicted as crucial for the protein function.
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Acknowledgments
This work was supported by the European Research Council (ERC Starting Grant 260888 to EMV). We are grateful to Dr. Andrea Poretti for the critical reading of the manuscript and revision of brain imaging and to Ms. Romina Cutigni for her technical assistance.
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Micalizzi, A., Moroni, I., Ginevrino, M. et al. Very mild features of dysequilibrium syndrome associated with a novel VLDLR missense mutation. Neurogenetics 17, 191–195 (2016). https://doi.org/10.1007/s10048-016-0488-y
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DOI: https://doi.org/10.1007/s10048-016-0488-y