Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literatures review

Abstract

Background 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. Methods A pedigree with A-T and predominant dystonia were collected. Genetic testing of the proband were performed by target exome-sequencing of a panel designed to cover 101 genes associated with movement disorders. The candidate variants were further confirmed by Sanger sequencing.Results Two novel ATM variants (p.I2683T and p.S2860P) with probable pathogenicity were identified in the family. The proband presented obviously isolated segmental dystonia without any signs of ataxia and telangiectasias. 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. Conclusion 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.