ATAXIA WITH OPHTHALMOPLEGIA OR SENSORY NEUROPATHY IS FREQUENTLY CAUSED BY POLG MUTATIONS

Abstract

Progress in molecular genetics unraveled the genetic basis of many subtypes of hereditary ataxias. Dominantly inherited forms are most frequently caused by CAG repeat expansions in the SCA1, SCA2, SCA3, SCA6, and SCA7 genes, whereas intronic GAA repeat expansions in the FRDA gene lead to Friedreich ataxia, the most common autosomal recessive ataxia in the Western world.1 Patients with ataxia who are negative for these mutations remain a major diagnostic challenge since genetic heterogeneity of ataxias is immense and includes a large number of extremely rare disorders.2 Phenotypic characteristics indicating the responsible gene are highly warranted to guide cost-intensive and time-intensive genetic screening. Patients with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) have been reported to carry mutations in the gene coding for DNA polymerase gamma ( POLG ).3–5 To analyze the indicative value of the SANDO phenotype for genetic diagnostics, we screened a cohort of ataxia patients with either external ophthalmoplegia or sensory neuropathy for POLG mutations. ### Methods. Twenty-six patients from 23 nonconsanguineous families with cerebellar ataxia plus sensory neuropathy or external ophthalmoplegia were included in this study. The whole coding region including intron-exon boundaries of the POLG gene was screened by direct sequencing. Primer sequences are noted in table e-1 on the Neurology ® Web site at www.neurology.org. Sensory neuropathy was clinically diagnosed in patients with reduced vibration sense, hyporeflexia at least of lower …