Session Information
Date: Tuesday, June 21, 2016
Session Title: Genetics (NON-PD)
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: This study includes the evaluation of a comprehensive spectrum of neurological features and the mutational screening of the SPG4/SPAST gene in patients with hereditary spastic paraplegia.
Background: Hereditary spastic paraplegia (HSP) includes a heterogeneous group of neurodegenerative disorders with the characteristics of slowly progressive spasticity and weakness of the lower limbs. Mutations in SPG4/SPAST represent the most frequent molecular etiology but the worldwide incidence is unknown.
Methods: A cohort of 726 patients, 98 sporadic and 628 subjects belonging to 215 families were recruited from Italian, Brazilian, and Japanese populations in a period from 2008 to 2015. Clinical and instrumental functional analyses consist of neurological assessment and neuroimaging. Mutational screening was carried out by PCR-direct sequencing and multiplex ligation dependent probe amplification. Haplotype studies were performed on three recurrent variants.
Results: Our study highlights clinical and epidemiological differences among the populations especially regarding age at onset and disability degree, showing unique genotype-phenotype correlations. Genetic analysis revealed a total of 52 different pathogenic nucleotide changes in 284 HSP patients: 21 sporadic cases and 263 cases from 96 families. Among them, six nucleotide changes are novel and pathogenic. The analysis revealed a great portion of private mutations worldwide and confirmed the founder effect for one recurrent variant in the Italian population. Interestingly, mutations were detected in 21% of sporadic cases, and in a range from 16% to 100% of families depending on the number of affected in the family.
Conclusions: This study represents the first worldwide SPG4/SPAST genetic screening on HSP patients. Epidemiological and clinical results broaden the spectrum of the clinical presentations of HSP associated with mutations in SPG4/SPAST. Finally, our findings provide evidence that the chance to detect SPG4/SPAST mutations varies proportionally to the number of affected in the family.
To cite this abstract in AMA style:
A. Orlacchio, M. Mearini, L. Pedace, A. Casella, C. Montecchiani, F. Gaudiello, M. Maurialuisa, R. Massa, C. Caltagirone, R.P. Munhoz, J.L. Pedroso, O.G.P. Barsottini, T. Kawarai. A clinico-genetical study in a large cohort of patients with spastic paraplegia type 4 (SPG4) [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/a-clinico-genetical-study-in-a-large-cohort-of-patients-with-spastic-paraplegia-type-4-spg4/. Accessed May 21, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-clinico-genetical-study-in-a-large-cohort-of-patients-with-spastic-paraplegia-type-4-spg4/