Spinocerebellar ataxia type 14 caused by a mutation in protein kinase C gamma.

BACKGROUND: We previously discovered spinocerebellar ataxia type 14 (SCA14) in a single Japanese family with an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia and intermittent axial myoclonus. The latter manifestation is selectively observed in patients with early onset. We mapped the locus to chromosome 19q13.4-qter, but the etiologic gene was not known. Recently, a mutation in the protein kinase C gamma gene (PRKCG) was identified in a US family of English and Dutch ancestry with autosomal dominant SCA whose disease mapped to a region overlapping that of the SCA14 locus. Different PRKCG mutations were found in another family with SCA and in a sporadic case from the United States. Axial myoclonus was not observed in any of these US families. OBJECTIVES: To determine whether a mutation in the PRKCG gene is responsible for SCA14 and to investigate the prevalence of PRKCG mutations in Japanese patients with autosomal dominant SCA. PATIENTS AND METHODS: Direct nucleotide sequencing analysis of the 18 coding exons of the PRKCG gene was performed in the 19 members of the original Japanese family with SCA14 and in 24 Japanese probands with SCA. After identifying a PRKCG mutation, DNA samples from 72 patients with multiple system atrophy and 50 healthy individuals were examined for the mutation as controls. RESULTS: Sequence analysis revealed a novel missense mutation, Gln127Arg, in all affected members of the family with SCA14. This mutation was not found in 122 control individuals. No mutations in the PRKCG gene were detected in the group of 24 probands with SCA of unknown type. CONCLUSIONS: These findings document that SCA14 is caused by mutations in the PRKCG gene. The observation that all 4 PRKCG mutations identified in patients with SCA to date are located in exon 4 suggests a critical role for this region of the gene in cerebellar function. Mutations in the same region of the gene can result in myoclonus in some families but not in others.

Dropped head sign as the only symptom of myasthenia gravis.

Neck extensor muscle weakness and the dropped head sign are associated with various neuromuscular disorders. However, these symptoms are comparatively rare in myasthenia gravis (MG). We report a MG case that presented with dropped head sign as the main symptom. A 55-year-old man developed subacute weakness of the neck extensor muscle and presented with dropped head. We established a diagnosis of MG based on the results of an edrophonium test and a voluntary single fiber electromyogram (vSFEMG), and a high serum antiacetylcholine receptor antibody level. This patient was treated with pyridostigmine and his neurological symptoms improved. There are reported cases of dropped head sign as the first symptom of MG, however, in those cases, other muscles showed weakness during the first few months after onset. In the present case, throughout the clinical course no other symptoms outside of dropped head sign were seen.