RFC1 and FGF14 Repeat Expansions in Serbian Patients with Cerebellar Ataxia.

Autor: Milovanović A; Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia., Dragaševic-Mišković N; Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia.; Medical Faculty, University Belgrade, Belgrade, Serbia., Thomsen M; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Borsche M; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.; Department of Neurology, University of Lübeck and University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Hinrichs F; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Westenberger A; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Klein C; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Brüggemann N; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.; Department of Neurology, University of Lübeck and University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Branković M; Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia., Marjanović A; Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia., Svetel M; Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia.; Medical Faculty, University Belgrade, Belgrade, Serbia., Kostić VS; Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia.; Medical Faculty, University Belgrade, Belgrade, Serbia., Lohmann K; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Jazyk: angličtina
Zdroj: Movement disorders clinical practice [Mov Disord Clin Pract] 2024 Jun; Vol. 11 (6), pp. 626-633. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1002/mdc3.14020
Abstrakt: Background: The newly discovered intronic repeat expansions in the genes encoding replication factor C subunit 1 (RFC1) and fibroblast growth factor 14 (FGF14) frequently cause late-onset cerebellar ataxia.
Objectives: To investigate the presence of RFC1 and FGF14 pathogenic repeat expansions in Serbian patients with adult-onset cerebellar ataxia.
Methods: The study included 167 unrelated patients with sporadic or familial cerebellar ataxia. The RFC1 repeat expansion analysis was performed by duplex PCR and Sanger sequencing, while the FGF14 repeat expansion was tested for by long-range PCR, repeat-primed PCR, and Sanger sequencing.
Results: We identified pathogenic repeat expansions in RFC1 in seven patients (7/167; 4.2%) with late-onset sporadic ataxia with neuropathy and chronic cough. Two patients also had bilateral vestibulopathy. Repeat expansions in FGF14 were found in nine unrelated patients (9/167; 5.4%) with ataxia, less than half of whom presented with neuropathy and two-thirds with global brain atrophy. Tremor and episodic features were the most frequent additional characteristics in carriers of uninterrupted FGF14 repeat expansions. Among the 122 sporadic cases, 12 (9.8%) carried an expansion in either RFC1 or FGF14, comparable to 4/45 (8.9%) among the patients with a positive family history.
Conclusions: Pathogenic repeat expansions in RFC1 and FGF14 are relatively frequent causes of adult-onset cerebellar ataxia, especially among sporadic patients, indicating that family history should not be considered when prioritizing ataxia patients for testing of RFC1 or FGF14 repeat expansions.
(© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE
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