Abstract
BackgroundSaccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2), nevertheless the heritability of this trait has not been properly demonstrated. Thus the present paper was aimed to assess the heritability of different saccadic parameters in SCA2.MethodsForty-eight SCA2 patients, 25 preclinical carriers and 24 non-SCA2 mutation carriers underwent electronystagmographical assessments of saccadic eye movements as well as neurological examination and ataxia scoring. Estimates of heritability based on the intraclass correlation coefficients were calculated for saccade velocity, accuracy and latency as well as for age at disease onset from 36, 17 and 15 sibling pairs of SCA2 patients, preclinical carriers and controls, respectively.ResultsSaccade velocity was significantly reduced in SCA2 patients and preclinical carriers, whereas decreased saccade accuracy and increased saccade latency were only observed in the patients cohort. Intraclass correlation coefficient for saccade velocity was highly significant in SCA2 patients, estimating a heritability around 94%, whereas for the age at ataxia onset this estimate was around 68%.ConclusionsElectronystagmographical measure of saccade velocity showed higher familial aggregation between SCA2 patients leading the suitability of this disease feature as endophenotype marker, with potential usefulness for the search of modifier genes and neurobiological underpinnings of the disease and as outcome measure in future neuroprotective clinical trials.
Highlights
Saccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2), the heritability of this trait has not been properly demonstrated
Endophenotype term has been only applied in the Spinocerebellar Ataxia type 2 (SCA2) [7]
It is known that SCA2 mutation carriers commonly show a conversion from deep tendon hyperreflexia to hyporeflexia even since late prodromal stage which is associated to the progression of sensory neuropathy [10]
Summary
Saccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2), the heritability of this trait has not been properly demonstrated. Endophenotype term has been only applied in the Spinocerebellar Ataxia type 2 (SCA2) [7] This autosomal dominant disease is caused by an unstable CAG repeat expansion on a coding. SCA2 patients present a progressive cerebellar syndrome, usually accompanied by a combination of other non-cerebellar features such as slow saccades, peripheral neuropathy and others [8, 9]. Several of these non-cerebellar clinical characteristics appear before the ataxia onset and define the prodromal stage of the disease [10, 11]. SCA2 reaches the worldwide highest prevalence in Holguín, Cuba, as result of a founder effect [12, 13], identifying the Cuban SCA2 population as a homogeneous resource for genetic studies
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