Identification of a novel mutation in the APTX gene associated with ataxia-oculomotor apraxia

Abstract

Hereditary ataxias are a clinically and genetically heterogeneous family of disorders defined by the inability to control gait and muscle coordination. Given the nonspecific symptoms of many hereditary ataxias, precise diagnosis relies on molecular genetic testing. To this end, we conducted whole-exome sequencing (WES) on a large consanguineous Iranian family with hereditary ataxia and oculomotor apraxia. WES in five affected and six unaffected individuals resulted in the identification of a homozygous novel stop-gain mutation in the APTX gene (c.739A>T; p.Lys247*) that segregates with the phenotype. Mutations in the APTX (OMIM 606350) gene are associated with ataxia with oculomotor apraxia type 1 (OMIM 208920).

Keywords: apraxia; ataxia; athetosis; progressive cerebellar ataxia.

Figure 1.

Pedigree of a consanguineous Iranian family with hereditary ataxia. Red boxes denote affected individuals. Boxes with asterisks indicate individuals who were analyzed by whole-exome sequencing.

Figure 2.

Sanger sequencing of family members reveal that the variant c.739A>T mutation segregates within the family among the affected and healthy controls. Note that Sanger sequencing was performed using a reverse primer. The genotype for affected individuals is T/T, whereas for healthy individuals it is A/A or T/A.