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De novo mutation in the GNAL gene causing seemingly sporadic dystonia in a Serbian patient
Author(s) -
Dobričić Valerija,
Kresojević Nikola,
Westenberger Ana,
Svetel Marina,
Tomić Aleksandra,
Ralić Vesna,
Petrović Igor,
Lukić Milica Ječmenica,
Lohmann Katja,
Novaković Ivana,
Klein Christine,
Kostić Vladimir S.
Publication year - 2014
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25876
Subject(s) - dystonia , mutation , sanger sequencing , genetics , medicine , cervical dystonia , genetic counseling , genetic testing , gene , biology , psychiatry
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