Clinical features of ataxia with oculoapraxia type 2 in China

Abstract

Background: Ataxia with oculomotor apraxia type 2 (AOA2) is very rare in China. This study aims to report on a Chinese girl with AOA2, and summarize the characteristics of Chinese AOA2 patients previously reported. Methods: We compiled a series of seven previously reported and one novel ataxic patients who underwent senataxin gene (SETX) sequencing because of suspected AOA2. The clinical and molecular features of a series of Chinese AOA2 patients with proven SETX mutations were summarized. Results: A novel homozygous missense mutation c.3455T>G (p.Phe1152Cys) in SETX was identified in a 17-year-old girl with ataxia, tremor, cervical dystonia and significantly elevated level of AFP (346 ng/mL). We reviewed a series of eight Chinese AOA2 patients from five families, including two males and six females. Onset of the disease occurred at an average age of 15.1 years, ranging from 10 to 20 years. The disease duration ranged from 3 to 24 years. The initial symptom was cerebellar ataxia in all cases (100%). Slurred speech and gaze nystagmus were present in six subjects (75%). None of the patients had OMA (0). One patient showed mild mental decline (12.5%). Cerebellar atrophy, pes cavus and polyneuropathy were found in 7 out of 8 cases (87.5%). Raised serum AFP levels were detected in five patients (62.5%). Extrapyramidal symptoms were found in three subjects (37.5%). Early-onset menopause was reported in one patient (12.5%). Five new mutations in the SETX were identified by molecular analyses. Among the variants, 10 homozygous or compound heterozygous variants in SETX were exonic, comprising 6 missense mutations, 2 nonsense mutations, 2 frameshift mutations. Conclusions: This is the first reported AOA2 case in China, exhibiting tremor, cervical dystonia and high AFP, which broadens the spectrum of Chinese AOA2. The phenotype of Chinese AOA2 shows a higher frequency of pes cavus, lower percentage of AFP elevation and the absence of OMA in comparison with AOA2 patients worldwide. Future studies in a larger cohort are needed to validate these findings.