Identification and characterization of novel PDYN mutations in dominant cerebellar ataxia cases.

Justyna Jezierska, Giovanni Stevanin, Hiroyuki Watanabe, Michiel R. Fokkens, Fabien Zagnoli, Jérôme Kok, Jean-Yves Goas, Pierre Bertrand, Christophe Robin, Alexis Brice, Georgy Bakalkin, Alexandra Durr, Dineke S. Verbeek
J Neurol. 2013-03-08; 260(7): 1807-1812
DOI: 10.1007/s00415-013-6882-6

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1. J Neurol. 2013 Jul;260(7):1807-12. doi: 10.1007/s00415-013-6882-6. Epub 2013 Mar

Identification and characterization of novel PDYN mutations in dominant
cerebellar ataxia cases.

Jezierska J(1), Stevanin G, Watanabe H, Fokkens MR, Zagnoli F, Kok J, Goas JY,
Bertrand P, Robin C, Brice A, Bakalkin G, Durr A, Verbeek DS.

Author information:
(1)Department of Genetics, University of Groningen, University Medical Center
Groningen, Oostersingel Entrance 47, P.O. Box 30 001, 9700 RB Groningen, The

We have recently identified missense mutations in prodynorphin (PDYN), the
precursor to dynorphin opioid peptides, as the cause for spinocerebellar ataxia
(SCA23) in Dutch ataxia cases. We report a screen of PDYN for mutations in 371
cerebellar ataxia cases, which had a positive family history; most are of French
origin. Sequencing revealed three novel putative missense mutations and one
heterozygous two-base pair deletion in four independent SCA patients. These
variants were absent in 400 matched controls and are located in the highly
conserved dynorphin domain. To resolve the pathogenicity of the heterozygous
variants, we assessed the peptide production of the mutant PDYN proteins. Two
missense mutations raised dynorphin peptide levels, the two-base pair deletion
terminated dynorphin synthesis, and one missense mutation did not affect PDYN
processing. Given the outcome of our functional analysis, we may have identified
at least two novel PDYN mutations in a French and a Moroccan SCA patient. Our
data corroborates recent work that also showed that PDYN mutations only account
for a small percentage (~0.1 %) of European SCA cases.

DOI: 10.1007/s00415-013-6882-6
PMID: 23471613 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus