TY - JOUR
T1 - Genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome
T2 - A Next Generation Sequencing study
AU - Picillo, Marina
AU - Ginevrino, Monia
AU - Dati, Giovanna
AU - Scannapieco, Sara
AU - Vallelunga, Annamaria
AU - Siano, Pietro
AU - Volpe, Giampiero
AU - Ceravolo, Roberto
AU - Nicoletti, Valentina
AU - Cicero, Edoardo
AU - Nicoletti, Alessandra
AU - Zappia, Mario
AU - Peverelli, Silvia
AU - Silani, Vincenzo
AU - Pellecchia, Maria Teresa
AU - Valente, Enza Maria
AU - Barone, Paolo
N1 - Copyright © 2021. Published by Elsevier Ltd.
PY - 2021/2/2
Y1 - 2021/2/2
N2 - OBJECTIVE: To perform the genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome.METHODS: A Next Generation Sequencing - based targeted sequencing of 32 genes associated to various neurodegenerative phenotypes, plus a screening for SNCA Copy Number Variations and C9orf72 repeat expansion, was applied in a cohort of 85 Italian patients presenting with parkinsonism and cognitive and/or behavioral syndrome and a positive familial history for any neurodegenerative disorder (i.e., dementia, movement disorders, amyotrophic lateral sclerosis).RESULTS: Through this combined genetic approach, we detected potentially relevant genetic variants in 25.8% of patients with familial parkinsonism and cognitive and/or behavioral syndrome. Peculiar phenotypes are described (Cortico-basal syndrome with APP, Posterior Cortical Atrophy with GBA, Progressive Supranuclear Palsy-like with GRN, Multiple System Atrophy with TARDBP). The majority of patients presented a rigid-bradykinetic parkinsonian syndrome, while rest tremor was less common. Myoclonic jerks, pyramidal signs, dystonic postures and vertical gaze disturbances were more frequently associated with the presence of a pathogenic variant in one of the tested genes.CONCLUSIONS: Given the syndromic approach adopted in our study, we were able to provide a detailed clinical description of patients beyond the boundaries of specific clinical diagnoses and describe peculiar phenotypes. This observation further supports the knowledge that genetic disorders present phenotypic overlaps across different neurodegenerative syndromes, highlighting the limitations of current clinical diagnostic criteria defining sharp boundaries between distinct conditions.
AB - OBJECTIVE: To perform the genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome.METHODS: A Next Generation Sequencing - based targeted sequencing of 32 genes associated to various neurodegenerative phenotypes, plus a screening for SNCA Copy Number Variations and C9orf72 repeat expansion, was applied in a cohort of 85 Italian patients presenting with parkinsonism and cognitive and/or behavioral syndrome and a positive familial history for any neurodegenerative disorder (i.e., dementia, movement disorders, amyotrophic lateral sclerosis).RESULTS: Through this combined genetic approach, we detected potentially relevant genetic variants in 25.8% of patients with familial parkinsonism and cognitive and/or behavioral syndrome. Peculiar phenotypes are described (Cortico-basal syndrome with APP, Posterior Cortical Atrophy with GBA, Progressive Supranuclear Palsy-like with GRN, Multiple System Atrophy with TARDBP). The majority of patients presented a rigid-bradykinetic parkinsonian syndrome, while rest tremor was less common. Myoclonic jerks, pyramidal signs, dystonic postures and vertical gaze disturbances were more frequently associated with the presence of a pathogenic variant in one of the tested genes.CONCLUSIONS: Given the syndromic approach adopted in our study, we were able to provide a detailed clinical description of patients beyond the boundaries of specific clinical diagnoses and describe peculiar phenotypes. This observation further supports the knowledge that genetic disorders present phenotypic overlaps across different neurodegenerative syndromes, highlighting the limitations of current clinical diagnostic criteria defining sharp boundaries between distinct conditions.
U2 - 10.1016/j.parkreldis.2021.01.024
DO - 10.1016/j.parkreldis.2021.01.024
M3 - Article
C2 - 33601107
VL - 84
SP - 82
EP - 90
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -