SCA27B is caused by an abnormal expansion of a GAA repeat located in the fibroblast growth factor 14 (FGF14) gene.
Diagnosis is established in an individual with suggestive symptoms and signs by the identification of a GAA expansion in FGF14. Expansions of more than 300 GAA repeats are generally considered disease-causing, whereas smaller expansions of 250-300 GAA repeats are likely to be disease-causing although may not cause disease in all persons (reduced penetrance). The disease is not thought to be caused by expansion with less than 250 repeats.
SCA27B is inherited in an autosomal dominant manner, which means that each child of an affected parent has a 50% probability of inheriting the disease. However, the repeat may vary significantly between generations and, usually, the number of copies tend to increase when inherited from the mother and decrease when inherited from the father. As a result, the parents of a patient may sometimes be asymptomatic, especially if the expanded copy is inherited from the mother. Conversely, an affected father may pass a smaller copy of the gene that is not disease-causing to his children.
FGF14