Spinocerebellar ataxia type 8

Abstract

The biologic relationship between repeat length and ataxia indicates that the CTG repeat is directly involved in SCA8 pathogenesis. Diagnostic testing and genetic counseling are complicated by the reduced penetrance, which often makes the inheritance appear recessive or sporadic, and by interfamilial differences in the length of a stable (CTA)n tract preceding the CTG repeat.

Molecular genetics of spinocerebellar ataxia type 8 (SCA8)

“…Clinical and molecular analysis of over 200 individuals from 25 different SCA8 ataxia families from our collection and from the literature Day et al, 2000;Juvonen et al, 2000;Silveira et al, 2000;Brusco et al, 2002;Topisirovic et al, 2002) demonstrate that SCA8 consistently presents as a very slowly progressive ataxia that largely spares brainstem and cerebral function. Affected individuals have gait, limb, speech and oculomotor incoordination, spasticity, and sensory loss.…”

“…Affected individuals have gait, limb, speech and oculomotor incoordination, spasticity, and sensory loss. In the largest SCA8 family reported to date (MN-A) the onset of gait abnormalities ranged from 13-60 years, and the age at which affected individuals needed a cane or a walker ranged from 35-50 years, with no one requiring a wheelchair prior to 45 years (Day et al, 2000). No affected MN-A family member with disease duration !…”

Eye Movement Abnormalities in Spinocerebellar Ataxias

“…SCA5 is characterized by eye abnormalities owing to cerebellar impairments such as downbeat nystagmus and impaired smooth pursuit movements (Ranum et al, 1994;Ikeda et al, 2002). Similar features occur in SCA8, in addition to saccadic dysmetria (Day et al, 2000;Koob et al, 1999), and SCA10 (Zu et al, 2000;Grewal et al, 2002;Lin & Ashizawa, 2005). SCA11 is associated with horizontal and vertical nystagmus as well as jerky pursuit (Worth et al, 1999), while approximately one third of SCA12 patients can develop saccadic slowing, abnormal smooth pursuits or pathological nystagmus (Worth et al, 1999, Fujigasaki et al, 2001.…”

Molecular Analysis of CTG/CTA Repeats at SCA8 Locus in South Indian Population

“…The existence of an antisense transcript, encoding a novel actin-binding protein (KLHL1), has recently been reported [17,18] suggesting that the pathogenic effect of SCA8 expansion may result in an alteration of KLHL1 messenger RNA stability or processing. However, the role of CTG expansion in the pathogenesis of SCA8 and the molecular mechanism responsible for the disease remain to be clarified [19]. SCA8 form of ataxia accounts for 2-5% of ADAs.…”