Rare sequence variants in ANO3 and GNAL in a primary torsion dystonia series and controls

Rare autosomal-dominant mutations in ANO3 and GNAL have been recently shown to represent novel genetic factors underlying primary torsion dystonia (PTD) with predominantly craniocervical involvement.

We used high-resolution melting to screen all exons of ANO3 and GNAL for rare sequence variants in a population of 342 German individuals with mainly sporadic PTD and 376 general population controls.

We identified 2 novel missense variants in ANO3 (p.Ile833Val and p.Gly973Arg) and 1 novel missense variant in GNAL (p.Val146Met) in three different nonfamilial cases. Variant carriers presented with adult-onset dystonia involving the neck and/or face. In controls, 3 rare ANO3 missense variants (p.Tyr235Cys, p.Asn256Ser, and p.Pro893Leu) but no rare nonsynonymous GNAL variants were present.

GNAL variants seem to be a rare cause of PTD in our mainly sporadic German sample. Low frequency missense variants in ANO3 occur in both cases and controls, warranting further assessment of this gene in PTD pathogenesis.