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Clinical and genetic investigation of the epsilon-sarcoglycan complex in neurologic and psychiatric disease

Peall, Kathryn J. ORCID: 2012. Clinical and genetic investigation of the epsilon-sarcoglycan complex in neurologic and psychiatric disease. PhD Thesis, Cardiff University.
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Myoclonus Dystonia Syndrome is a childhood onset hyperkinetic movement disorder characterised by alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene, which encodes the transmembrane epsilon-sarcoglycan protein. Previous studies suggest an increased rate of psychiatric disorders in those with SGCE mutations. This study aimed to establish a cohort of myoclonus dystonia syndrome patients, identify the rate and type of SGCE mutations, determine differences in motor characteristics between mutation positive and negative cases and whether psychiatric disorders form part of the disease phenotype. Eighty-nine probands with clinically suspected MDS were recruited. Information regarding onset and distribution of motor symptoms was collected via systematic questionnaires and video taped examination. SGCE was analysed using direct sequencing and for copy number variants. Psychiatric symptoms were assessed using systematic and standardised questionnaires and compared to a disability-matched, alcohol responsive tremor control group. Nineteen (21%) probands had an SGCE mutation. All had evidence of upper body predominant myoclonus and dystonia during their disease course. Five had contiguous gene deletions ranging from 0.7 to 2.3Mb in size with distinctive clinical features. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive-Compulsive Disorder was eight times more likely (p<0.001) in mutation positive cases, compulsivity being the predominant feature (p<0.001). Generalized Anxiety Disorder (p=0.003) and alcohol dependence (p=0.02) were five times more likely in cases than tremor controls. Overall, SGCE mutations are associated with a narrow clinical and specific psychiatric phenotype. The presence of myoclonus, dystonia, age at onset ≤10 years and a positive family history of the disorder are the strongest predictors of an SGCE mutation. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Funders: Welsh Clinical Academic Traack Program
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Oct 2023 14:37

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