Rare sequence variants in ANO3 and GNAL in a primary torsion dystonia series and controls. Issue 1 (22nd October 2013)

• Record Type: Journal Article
• Authors: Zech, Michael; Gross, Nadine; Jochim, Angela; Castrop, Florian; Kaffe, Maria; Dresel, Christian; Lichtner, Peter; Peters, Annette; Gieger, Christian; Meitinger, Thomas; Haslinger, Bernhard; Winkelmann, Juliane
• Is Part Of: Movement disorders. Volume 29:Issue 1(2013)
• Page Start: 143
• Page End: 147
• Publication Date: 2013-10-22
• Subjects: Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.25715
• Languages: English
• ISSNs: 0885-3185

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="mds25715-sec-0001" sec-type="section"> <title>Background</title> <p>Rare autosomal‐dominant mutations in <italic>ANO3</italic> and <italic>GNAL</italic> have been recently shown to represent novel genetic factors underlying primary torsion dystonia (PTD) with predominantly craniocervical involvement.</p> </sec> <sec id="mds25715-sec-0002" sec-type="section"> <title>Methods</title> <p>We used high‐resolution melting to screen all exons of <italic>ANO3</italic> and <italic>GNAL</italic> for rare sequence variants in a population of 342 German individuals with mainly sporadic PTD and 376 general population controls.</p> </sec> <sec id="mds25715-sec-0003" sec-type="section"> <title>Results</title> <p>We identified 2 novel missense variants in <italic>ANO3</italic> (p.Ile833Val and p.Gly973Arg) and 1 novel missense variant in <italic>GNAL</italic> (p.Val146Met) in three different nonfamilial cases. Variant carriers presented with adult‐onset dystonia involving the neck and/or face. In controls, 3 rare <italic>ANO3</italic> missense variants (p.Tyr235Cys, p.Asn256Ser, and p.Pro893Leu) but no rare nonsynonymous <italic>GNAL</italic> variants were present.</p> </sec> <sec id="mds25715-sec-0004" sec-type="section"> <title>Conclusions</title> <p> <italic>GNAL</italic> variants seem to be a rare cause of PTD in our mainly sporadic German sample. Low frequency missense variants in <italic>ANO3</italic> occur in both cases and controls, warranting further assessment of this gene in PTD pathogenesis. © 2013 International Parkinson and Movement Disorder Society</p> </sec> </abstract>