Prrt2 is a neuron-specific protein expressed at axonal and pre-synaptic domains, involved in synaptic neurotransmitter release and modulation of intrinsic excitability. Mutations in PRRT2 cause a spectrum of autosomal dominant paroxysmal neurological disorders including epilepsy, movement disorders, and hemiplegic migraine and show incomplete penetrance and variable expressivity. We assessed the diagnostic rate of PRRT2 in a cohort of Italian patients with epilepsy and/or paroxysmal kinesigenic dyskinesia (PKD) and evaluated genotype-phenotype correlations. Clinical data were collected using a structured questionnaire. Twenty-seven out of 55 (49.1%) probands carried PRRT2 heterozygous pathogenic variants, including six previously known genotypes and one novel missense mutation. A family history of epilepsy starting in the first year of life and/or PKD was strongly suggestive of a PRRT2 pathogenic variant. Epilepsy patients harbouring PRRT2 pathogenic variants showed earlier seizure onset and more frequent clusters compared with PRRT2-negative individuals with epilepsy. Moreover, we did also identify individuals with PRRT2 pathogenic variants with atypical age at onset, i.e. childhood-onset epilepsy and infantile-onset PKD. However, the lack of a clear correlation between specific PRRT2 genotypes and clinical manifestations and the high incidence of asymptomatic carriers suggest the involvement of additional factors in modulating expressivity of PRRT2-related disorders. Finally, our study supports the pleiotropic and multifaceted physiological role of PRRT2 gene which is emerging from experimental neuroscience.
Clinical spectrum and genotype-phenotype correlations in PRRT2 Italian patients / G. Balagura, A. Riva, F. Marchese, M. Iacomino, F. Madia, T. Giacomini, M.M. Mancardi, E. Amadori, M.S. Vari, V. Salpietro, A. Russo, T. Messana, A. Vignoli, V. Chiesa, L. Giordano, P. Accorsi, L. Caffi, A. Orsini, A. Bonuccelli, M. Santucci, M. Vecchi, F. Vanadia, G. Milito, C. Fusco, G. Cricchiutti, M. Carpentieri, L. Margari, A. Spalice, F. Beccaria, F. Benfenati, F. Zara, P. Striano. - In: EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY. - ISSN 1090-3798. - 28(2020 Sep 28), pp. 193-197.
|Titolo:||Clinical spectrum and genotype-phenotype correlations in PRRT2 Italian patients|
|Parole Chiave:||Epilepsy; Genetics; Paroxysmal dyskinesia; PRRT2|
|Settore Scientifico Disciplinare:||Settore MED/39 - Neuropsichiatria Infantile|
|Data di pubblicazione:||28-set-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ejpn.2020.06.005|
|Appare nelle tipologie:||01 - Articolo su periodico|