Two Novel Heterozygote Mutations of ATM in a Chinese Family with Dystonia-Dominant Ataxia Telangiectasia and Literatures Review

Abstract Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, mainly including classic A-T and milder forms. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T, including ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifested as isolated dystonia without any signs of classical A-T. To date, more than 400 disease-related ATM mutations have been identified in patients with A-T. In this study, target exome-sequencing was performed in an AT pedigree with predominant dystonia. Two novel ATM mutations, p.I2683T and p.S2860P, were identified in the family. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T. To our knowledge, this is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. ATM genetic testing should be early considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.