Journal Article

Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Ory-Magne Fabienne, Calmels Nadège, Renaud Mathilde, Casenave Philippe, Chelly Jamel, Pische Guillaume, Tison François, Bossenmeyer-Pourié Carine, Koenig, Michel, Ewenczyk Claire, Halleb Yosra, Oussalah Abderrahim, Tranchant, Christine, Benkirane Mehdi, Chaussenot Annabelle, Drouot Nathalie, Marelli, Cecilia, Bonnet Céline, Leheup Bruno, Frismand Solène, Tyvaert Louise, Ravel Jean-Marie, Lecocq, Claire, Larrieu Lise, Pointaux Morgane, Anheim Mathieu, Lambert Laëtitia, Jean-Louis, Guéant

2021

Overview

BackgroundSTUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1 are now considered a frequent cause of cerebellar ataxia.ObjectiveWe aimed to improve the clinical, radiological, and molecular delineation of SCAR16 and SCA48.MethodsRetrospective collection of patients with SCAR16 or SCA48 diagnosed in three French genetic centers (Montpellier, Strasbourg and Nancy).ResultsHere, we report four SCAR16 and nine SCA48 patients from two SCAR16 and five SCA48 unrelated French families. All presented with slowly progressive cerebellar ataxia. Additional findings included cognitive decline, dystonia, parkinsonism and swallowing difficulties. The age at onset was highly variable, ranging from 14 to 76 years. Brain MRI showed marked cerebellar atrophy in all patients. Phenotypic findings associated with STUB1 pathogenic variations cover a broad spectrum, ranging from isolated slowly progressive ataxia to severe encephalopathy, and include extrapyramidal features. We described five new pathogenic variations, two previously reported pathogenic variations, and two rare variants of unknown significance in association with STUB1-related disorders. We also report the first pathogenic variation associated with both dominant and recessive forms of inheritance (SCAR16 and SCA48).ConclusionEven though differences are observed between the recessive and dominant forms, it appears that a continuum exists between these two entities. While adding new symptoms associated with STUB1 pathogenic variations, we insist on the difficulty of genetic counselling in STUB1-related pathologies. Finally, we underscore the usefulness of DAT-scan as an additional clue for diagnosis.

• Publisher: Springer Nature B.V
• Subject: Ataxia / Atrophy / Basal ganglia / Central nervous system diseases / Cerebellar ataxia / Cerebellum / Cognitive ability / Dystonia / Encephalopathy / Genetic counseling / Heredity / Homology / Magnetic resonance imaging / Movement disorders / Neurology