Gene/phenotype/disorder under study
Gene NPTX1 (OMIM *620158)/ Spinocerebellar ataxia 50
Abstract
NPTX1 variants were first described as a new cause of autosomal dominant spinocerebellar ataxia type 50 (SCA50) in 2022. The most common presentation of NPTX1-related disorder is late-onset ataxia. However, one case of early-onset ataxia associated with epilepsy has also been reported.
Monoallelic NPTX1 variants are associated with a broad phenotypic spectrum, predominantly characterized by cerebellar ataxia, oculomotor apraxia, dystonia and tremor. Additional clinical features include chorea, myoclonus, nystagmus (including downbeat nystagmus), square-wave jerks, dysarthria, dysphagia, cognitive impairment, epileptic seizures, diplopia, and hearing loss. Brain MRI typically shows cerebellar atrophy. In some cases, white matter abnormalities and brain iron accumulation have also been documented.
Our goal is to conduct a comprehensive pheno-genotypic analysis and to define the natural history of NPTX1-related disorder variants in a large international patient cohort.
Coordinating clinicians
Dr Francesca Magrinelli – f.magrinelli@ucl.ac.uk
Institutions
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: Yes (not mandatory)
2- Resampling of patients: Yes (not mandatory)
3- Linked to a translational/basic research project: No