Category: Ataxia
Objective: To evaluate the diagnosis rate of Next Generation Sequencing (NGS) in a combined series of patients with progressive cerebellar ataxia (CA) and progressive spastic paraplegia (SPG), with suspected genetic etiology, under follow-up in a Movement Disorders Unit of the HUVR, in Seville, Spain.
Background: CA and SPG represent the extremes of the same spectrum of neurodegenerative diseases. Nowdays there are more than 200 genes related to these disorders. Achieving a confirmed genetic diagnosis remains a challenge, although the emergence of NGS studies in recent decades has had a great impact on the diagnosis of these patients.
Method: 296 patients (174 CA and 122 SPG) from 246 families were included. NGS studies were classified as: target sequencing (TS) and whole exome sequencing (WES). The results of NGS studies were classified as follows: Positive (genetic confirmation), Negative (no significant findings), or Inconclusive (variants of unknown significant (VUS) found).
Results: 121 TG studies were performed: 72 from the CA series and 49 from the SPG series. 47 WES were performed: 22 of the CA series and 25 of the SPG series. The result was Positive in 21 TS and 5 WES of the CA series, and 17 TS and 10 WES of the SPG series. Features as positive family history and early onset rised the possibilities for positive results for both TS and WES, however, sporadic cases also were diagnosed, 14 through TS and 8 through WES. The percentage of patients with diagnostic confirmation in the CA series rised from 36.2% in the pre-NGS era to 48.27% with TS studies and 51.14% with WES studies. For the SPG series, the percentage of patients with diagnostic confirmation rised from 53.22% in the pre-NGS era to 66.93% with TS studies and 75% with WES studies.
Conclusion: After performing NGS techniques in a series of CA and SPG with a suspected genetic cause, the percentage of cases with diagnostic confirmation were significantly raised in both, CA and SPG
To cite this abstract in AMA style:
A. Adarmes Gómez, S. Jesús Maestre, D. Macias Garcia, F. Carrillo Garcia, L. Muñoz Delgado, P. Gómez Garre, P. Mir. NGS diagnosis rate in a combined cerebellar ataxia and spastic paraplegia series from southern Spain [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/ngs-diagnosis-rate-in-a-combined-cerebellar-ataxia-and-spastic-paraplegia-series-from-southern-spain/. Accessed May 9, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/ngs-diagnosis-rate-in-a-combined-cerebellar-ataxia-and-spastic-paraplegia-series-from-southern-spain/