Characteristics of a Cohort of Individuals With SCA27B Associated With Repeat Expansions in FGF14

Abstract

Objectives Spinocerebellar ataxia 27B (SCA27B) is a recently discovered genetic cause of idiopathic late-onset cerebellar ataxia (ILOCA) due to guanine-adenine-adenine (GAA) repeat expansions (greater than 250) in FGF14. We aimed to identify and characterize a New Zealand cohort of patients with SCA27B. Methods Patients with previous negative ataxia panels were identified from electronic records and tested with an updated ataxia repeat expansion panel including FGF14 and 5 other new genes. Results Updated genetic testing for 11 of the 29 patients returned a positive result: repeat expansions in FGF14 in 9, RFC1 (associated with cerebellar ataxia, neuropathy, vestibular areflexia syndrome) in 1, and TBP (associated with SCA17) in 1. In the 9 patients with SCA27B, the clinical characteristics such as initial episodic symptoms and late age at onset (mean 56 years), were like those reported in European cohorts. Two patients in our cohort had palatal tremor. While 7 patients had a repeat expansion length greater than 250, 2 patients with a clinical phenotype consistent with SCA27B had between 200 and 250 repeats. Discussion In our New Zealand cohort of patients with ILOCA, updated genetic testing revealed a diagnosis in 38%. SCA27B is a common cause of ILOCA in this cohort.