Dominant Ataxias: Medical and Scientific Update.

Editors Note: Reprinted with permission of Euro-Ataxia.

This update is based on the presentation during this year's AGM in Valjeviken Rehabilitation Centre, beautifully situated on the south coast of Sweden. In last year's update on dominant ataxia's, I could mention the identification of four new SCA's (SpinoCerebellar Ataxia's): SCA8, SCA10, SCA11 and SCA12. Since then, another two SCA's have been added: SCA13 and SCA14. Although perhaps no major breakthroughs have been achieved, progress in understanding the mechanisms of damage and death of nerve cells in dominant ataxia and other neurodegenerative disorders is well ongoing. It is the aim of this communication to summarize the main achievements in the past year.

Genetics

With the number of genetically identified SCA's still increasing, this year SCA13 and SCA14 have been identified. SCA13 was found in a single French family and was reported last July by the group from La Salpetriere in Paris. In this family, affected members showed slowly progressive cerebellar gait ataxia and dysarthria with onset in childhood, delayed motor milestones and moderate mental retardation. Some of them also showed signs of spasticity and disturbed eye movements (nystagmus), and MRI imaging in two patients demonstrated moderate cerebellar and pontine atrophy. After exclusion of known SCA mutations and SCA loci in this family, a genome wide search showed linkage to a new locus on chromosome 19q13.3-q13.4. The gene itself has not yet been identified.

One month later, in August 2000, SCA14 was reported in a three generation Japanese family by the group from Sapporo. In this family, progressive ataxia started in adult life. Affected people with a relatively late age at onset (beyond 38 years) showed only cerebellar ataxia, but those with a relatively early onset (before 28 years), showed an initial stage with intermittent myoclonus before the manifestation of progressive ataxia. Imaging studies in a few members showed cerebellar atrophy without brainstem involvement. A genome wide search linked the disorder in this family to a locus on chromosome 19q13.4-qter. It is intriguing that the SCA13 and SCA14 loci are on the same chromosome 19q, and are actually neighboring each other on either side of chr19q13.4. Although clinical manifestations in the two families obviously differ, the close proximity of their loci suggests the possibility that they might be genetically similar. This reminds of the situation some six years ago, when the gene for SCA3 was genetically localized in the same region of chromosome 6p as the gene for Machado Joseph's disease, but on clinical grounds was considered to be different, and later the CAG expansion in the MJD gene was also found in SCA3.

Very recently, in October, the gene mutation of SCA10 has been published by the same collaborating group from Houston and Los Angeles who described SCA10 last year in two Mexican-American families. As they predicted from the occurrence of anticipation, they found an unstable repeat expansion mutation as the genetic cause of …