Publications by authors named "Philippe Casenave"

3 Publications

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

J Neurol 2021 Jan 8. Epub 2021 Jan 8.

Service de Génétique Médicale, Hôpitaux de Brabois, CHRU de Nancy, Rue du Morvan, 54500, Vandoeuvre-lès-Nancy, France.

Background: STUB1 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.

Objective: We aimed to improve the clinical, radiological, and molecular delineation of SCAR16 and SCA48.

Methods: Retrospective collection of patients with SCAR16 or SCA48 diagnosed in three French genetic centers (Montpellier, Strasbourg and Nancy).

Results: Here, 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).

Conclusion: Even 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.
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http://dx.doi.org/10.1007/s00415-020-10348-xDOI Listing
January 2021

Severe Charcot-Marie-Tooth disease type 1E caused by a novel p.Phe84Leufs*24 PMP22 point mutation.

J Peripher Nerv Syst 2013 Jun;18(2):181-4

Institut des Maladies Neurodégénératives, CNRS UMR 5293, Université de Bordeaux, Bordeaux, France.

We report a severe phenotype of Charcot-Marie-Tooth (CMT) disease type 1E caused by a novel p.Phe84Leufs*24 PMP22 point mutation. Ultrastructural examination of a nerve biopsy showed non- or partly myelinated axons which were surrounded by "onion bulb" formations mainly composed of concentric basement membranes and characterized by the presence of prominent concentric or longitudinal collagen fibrils interspersed with basement membranes. PMP22 point mutations are rare and responsible for polyneuropathies often demyelinating with onion bulb formations composed of concentric and redundant basement membranes. Entrapment of prominent collagen fibrils within onion bulb formations is unusual, even in the large spectrum of CMT disease with long duration and severe damage.
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http://dx.doi.org/10.1111/jns5.12028DOI Listing
June 2013