Genetic screening of Greek patients with Huntington’s disease phenocopies identifies an SCA8 expansion.

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Huntington ’s disease (HD ) is an autosomal dominant disorder characterized by a triad of chorea , psychiatric disturbance and cognitive decline . Around 1 % of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies . Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL 1 , HDL 2 and HDL 4 (SCA 17 ), some spinocerebellar ataxias (SCAs ) and dentatorubral-pallidoluysian atrophy (DRPLA ). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL 2 , SCA 17 , SCA 1 , SCA 2 , SCA 3 ,SCA 8 , SCA 12 and DRPLA . Fifteen patients (71 %) had a positive family history . We identified one patient (4 .8 % of the total cohort ) with an expansion of 81 combined CTA /CTG repeats at the SCA 8 locus . This falls within what is believed to be the high -penetrance allele range . In addition to the classic HD triad , the patient had features of dystonia and oculomotor apraxia . There were no cases of HDL 2 , SCA 17 , SCA 1 , SCA 2 , SCA 3 , SCA 12 or DRPLA . Given the controversy surrounding the SCA 8 expansion , the present finding may be incidental . However , if pathogenic , it broadens the phenotype that may be associated with SCA 8 expansions . The absence of any other mutations in our cohort is not surprising , given the low probability of reaching a genetic diagnosis in HD phenocopy patients .