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

Authors


  • Funding agencies: This study was supported by grants from The Ministry of Education and Science, Republic of Serbia (projects #ON175090 [to VK] and #ON175091 [to IN]), and a grant from the Hermann and Lilly Schilling Foundation (to CK).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

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

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