Funding agencies: This work was supported by the Volkswagen Foundation (Lichtenberg Grant; to C.K.) and the Hermann and Lilly Schilling Foundation (to C.K.).
Article first published online: 28 SEP 2011
Copyright © 2011 Movement Disorder Society
Volume 26, Issue 13, pages 2404–2408, November 2011
How to Cite
Wilcox, R. A., Winkler, S., Lohmann, K. and Klein, C. (2011), Whispering dysphonia in an Australian family (DYT4): A clinical and genetic reappraisal. Mov. Disord., 26: 2404–2408. doi: 10.1002/mds.23866
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.
- Issue published online: 22 NOV 2011
- Article first published online: 28 SEP 2011
- Manuscript Accepted: 15 JUN 2011
- Manuscript Revised: 29 MAY 2011
- Manuscript Received: 6 APR 2011
- whispering dysphonia;
- Wilson disease
The designation, DYT4, was assigned to an Australian family with whispering dysphonia. The role of known causes of dystonia has not been comprehensively investigated in this family, nor has the possible relationship with Wilson disease (WND) in 2 siblings. Eighteen family members were neurologically examined, and DNA samples were obtained. Linkage analysis was performed to DYT1, DYT6, DYT7, DYT11, DYT13, DYT15, and ATP7B with microsatellite markers and the THAP1 (DYT6), PRKRA (DYT16), and ATP7B (WND) genes were sequenced. Reevaluation of the family identified 9 living affected family members, 6 of whom are newly affected. Phenotypic expression was variable, ranging from isolated spasmodic dysphonia (often with mild craniocervical dystonia) to severe generalized dystonia. Two newly described features included an extrusional tongue dystonia and a unique “hobby horse gait.” Genetic analyses excluded all tested loci. Haplotype analysis of the ATP7B region resulted in three different combinations of the two parental alleles in the 8 investigated siblings of the 2 deceased WND patients, indicating that the fourth combination (of two mutated alleles) had occurred only in the deceased WND patients. On these two alleles, we identified a missense (c.2297C>G; p.T766R) and a splice-site mutation (IVS5+1G>T). The c.2297C>G mutation was detected in 3 affected and 4 unaffected family members, whereas the IVS5+1G>T mutation was detected in 1 affected and unaffected family member. Five DYT4 patients carried neither mutation. DYT4 is a familial form of dystonia unrelated to known dystonia genes and loci. ATP7B mutations do not segregate with the dystonia phenotype, indicating two independent genetic diseases in this family. © 2011 Movement Disorder Society