A novel ANO3 variant identified in a 53-year-old woman presenting with hyperkinetic dysarthria, blepharospasm, hyperkinesias, and complex motor tics. BMC Med Genet 2016 Dec 05;17(1):93
Date
12/07/2016Pubmed ID
27919237Pubmed Central ID
PMC5139108DOI
10.1186/s12881-016-0354-7Scopus ID
2-s2.0-85000613296 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
BACKGROUND: Cervical dystonias have a variable presentation and underlying etiology, but collectively represent the most common form of focal dystonia. There are a number of known genetic forms of dystonia (DYT1-27); however the heterogeneity of disease presentation does not always make it easy to categorize the disease by phenotype-genotype comparison.
CASE PRESENTATION: In this report, we describe a 53-year-old female who presented initially with hand tremor following a total hip arthroplasty. The patient developed a mixed hyperkinetic disorder consisting of chorea, dystonia affecting the upper extremities, dysarthria, and blepharospasm. Whole exome sequencing of the patient revealed a novel heterozygous missense variant (Chr11(GRCh38): g.26525644C > G; NM_031418.2(ANO3): c.702C > G; NP_113606.2. p.C234W) in exon 7 in the ANO3 gene.
CONCLUSIONS: ANO3 encodes anoctamin-3, a Ca+2-dependent phospholipid scramblase expressed in striatal-neurons, that has been implicated in autosomal dominant craniocervical dystonia (Dystonia-24, DYT24, MIM# 615034). To date, only a handful of cases of DYT-24 have been described in the literature. The complex clinical presentation of the patient described includes hyperkinesias, complex motor movements, and vocal tics, which have not been reported in other patients with DYT24. This report highlights the utility of using clinical whole exome sequencing in patients with complex neurological phenotypes that would not normally fit a classical presentation of a defined genetic disease.
Author List
Blackburn PR, Zimmermann MT, Gass JM, Harris KG, Cousin MA, Boczek NJ, Ross OA, Klee EW, Brazis PW, Van Gerpen JA, Atwal PSAuthor
Michael T. Zimmermann PhD Director, Associate Professor in the Data Science Institute department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AbdomenAmino Acid Sequence
Anoctamins
Blepharospasm
Chloride Channels
Dysarthria
Dystonia
Electrophysiology
Exons
Female
Heterozygote
Humans
Hyperkinesis
Middle Aged
Molecular Sequence Data
Mutation, Missense
Pedigree
Polymorphism, Genetic
Sequence Alignment
Tics
