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Abstract
Objective: To determine the contribution of TUBB4A, recently associated with DYT4 dystonia in a pedigree with “whispering dysphonia” from Norfolk, United Kingdom, to the etiopathogenesis of primary dystonia.
Methods: High-resolution melting and Sanger sequencing were used to inspect the entire coding region of TUBB4A in 575 subjects with primary laryngeal, segmental, or generalized dystonia.
Results: No pathogenic variants, including the exon 1 variant (c.4C>G) identified in the DYT4 whispering dysphonia kindred, were found in this study.
Conclusion: The c.4C>G DYT4 mutation appears to be private, and clinical testing for TUBB4A mutations is not justified in spasmodic dysphonia or other forms of primary dystonia. Moreover, given its allelic association with leukoencephalopathy hypomyelination with atrophy of basal ganglia and cerebellum and protean clinical manifestations (chorea, ataxia, dysarthria, intellectual disability, dysmorphic facial features, and psychiatric disorders), DYT4 should not be categorized as a primary dystonia.
GLOSSARY
- EVS=
- Exome Variant Server;
- H-ABC=
- hypomyelination with atrophy of basal ganglia and cerebellum;
- HRM=
- high-resolution melting;
- MREI=
- methionine–arginine–glutamic acid–isoleucine;
- SNP=
- single nucleotide polymorphism
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received October 4, 2013.
- Accepted in final form December 29, 2013.
- © 2014 American Academy of Neurology
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