De novo mutation in the GNAL gene causing seemingly sporadic dystonia in a serbian patient.

BACKGROUND:  Mutations in GNAL (DYT25) have recently been established as the first confirmed cause of focal or segmental adult-onset dystonia. Mutation carriers show craniocervical involvement; however, the GNAL mutational and phenotypic spectrum remain to be further characterized, and guidelines for diagnostic testing need to be established. METHODS:  The authors used Sanger sequencing to test for changes in the GNAL coding or splice-site regions in 236 Serbian patients suffering from isolated dystonia with craniocervical involvement. RESULTS: One novel likely pathogenic substitution (c.1061T>C; p.Val354Ala) in GNAL was detected in a sporadic cervical dystonia patient (mutation frequency: 0.4%). This mutation was not present in the DNA of either parent, despite confirmed parentage. CONCLUSIONS: This is the first report of a de novo GNAL mutation causing genetically proven, seemingly sporadic DYT25 dystonia. Our finding highlights the importance of genetic testing for GNAL mutations in establishing the molecular diagnosis even for patients with a negative family history. © 2014 International Parkinson and Movement Disorder Society © 2014 International Parkinson and Movement Disorder Society.