259 A novel mutation of protein kinase C gamma associated with spinocerebellar ataxia type 14

Abstract

BackgroundSpinocerebellar ataxia (SCA) type 14 (SCA14) is an autosomal dominant neurodegenerative disorder caused by mutations in the protein kinase Cγ gene (PRKCG). It is a very rare form of autosomal dominant cerebellar ataxia (ADCA), accounting for approximately 1–4% of all cases.CaseWe present a patient with a typical SCA14 phenotype, who was found to have a novel mutation in the PRKCG gene (heterozygous for C.344A> T p. (ASP115VAL)), a 74 year old man who presented with a one year history of poor balance. Neurological examination revealed dysarthric speech in a cerebellar pattern, slight bilateral finger-nose dysmetria, dysdiadochokinesis, and significant heel-shin incoordina- tion. He walked with a wide-based gait and could not attempt tandem gait. Blood tests to exclude an underlying secondary cause for his ataxia were non-diagnostic. MRI brain revealed selective cerebellar atrophy with a minor degree of small vessel disease.Initial genetic testing did not reveal abnormality. An extended ataxia genetic panel testing of 98 genes known to cause ataxia revealed a novel mutation.DiscussionThis case adds to the number of novel missense mutations leading to a SCA14 phenotype. While current management of spinocerebellar ataxias is supportive, the importance of accurate diagnosis has become pertinent in recent years with emerging gene therapies.sara.leddy1@nhs.net