TY - JOUR
T1 - Episodic ataxia and severe infantile phenotype in spinocerebellar ataxia type 14: expansion of the phenotype and novel mutations
AU - De Michele, Giovanna
AU - Galatolo, Daniele
AU - Galosi, Serena
AU - Mignarri, Andrea
AU - Silvestri, Gabriella
AU - Casali, Carlo
AU - Leuzzi, Vincenzo
AU - Ricca, Ivana
AU - Barghigiani, Melissa
AU - Tessa, Alessandra
AU - Cioffi, Ettore
AU - Caputi, Caterina
AU - Riso, Vittorio
AU - Dotti, Maria Teresa
AU - Saccà, Francesco
AU - De Michele, Giuseppe
AU - Cocozza, Sirio
AU - Filla, Alessandro
AU - Santorelli, Filippo M.
PY - 2021
Y1 - 2021
N2 - Introduction: Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurological disorder characterized by slowly progressive cerebellar ataxia. SCA14 is caused by mutations in PRKCG, a gene encoding protein kinase C gamma (PKCγ), a master regulator of Purkinje cells development. Methods: We performed next-generation sequencing targeted resequencing panel encompassing 273 ataxia genes in 358 patients with genetically undiagnosed ataxia. Results: We identified fourteen patients in ten families harboring nine pathogenic heterozygous variants in PRKCG, seven of which were novel. We encountered four patients with not previously described phenotypes: one with episodic ataxia, one with a spastic paraparesis dominating her clinical manifestations, and two children with an unusually severe phenotype. Conclusions: Our study broadens the genetic and clinical spectrum of SCA14.
AB - Introduction: Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurological disorder characterized by slowly progressive cerebellar ataxia. SCA14 is caused by mutations in PRKCG, a gene encoding protein kinase C gamma (PKCγ), a master regulator of Purkinje cells development. Methods: We performed next-generation sequencing targeted resequencing panel encompassing 273 ataxia genes in 358 patients with genetically undiagnosed ataxia. Results: We identified fourteen patients in ten families harboring nine pathogenic heterozygous variants in PRKCG, seven of which were novel. We encountered four patients with not previously described phenotypes: one with episodic ataxia, one with a spastic paraparesis dominating her clinical manifestations, and two children with an unusually severe phenotype. Conclusions: Our study broadens the genetic and clinical spectrum of SCA14.
KW - Broadened phenotype
KW - NGS targeted resequencing panel
KW - Novel mutations
KW - PRKCG
KW - Spinocerebellar ataxia type 14
KW - Broadened phenotype
KW - NGS targeted resequencing panel
KW - Novel mutations
KW - PRKCG
KW - Spinocerebellar ataxia type 14
UR - http://hdl.handle.net/10807/182933
U2 - 10.1007/s00415-021-10712-5
DO - 10.1007/s00415-021-10712-5
M3 - Article
SN - 0340-5354
SP - 1476
EP - 1484
JO - Journal of Neurology
JF - Journal of Neurology
ER -