Novel ATM mutations with ataxia-telangiectasia

• We report three Chinese patients who demonstrated ataxia, oculomotor apraxia, choreoathetosis, myoclonus and telangiectasias of the eyes.
• Sequence analysis of ATM revealed two known missense mutations c.8287C > T and c.9139C > T in the siblings. Intrafamilial clinical heterogeneity was observed in the siblings.
• The other patient was compound heterozygote for ATM: c.8911C > T and c.7141_7151delAATGGAAAAAT, both of which were new and not found in 200 controls.
• This study widens the spectrum of mutations and phenotypes in ataxia telangiectasia.

Ataxia telangiectasia is an autosomal recessive multisystem disorder characterized by progressive cerebellar ataxia with onset in childhood, oculocutaneous telangiectasia, increased serum alpha-fetoprotein, immunodeficiency, chromosomal instability, and radiation hypersensitivity. Ataxia-telangiectasia mutated gene (ATM) is one of the known genes to be associated with ataxia telangiectasia. We reported the clinical and genetic findings of three early-onset Chinese patients who demonstrated ataxia, oculomotor apraxia, choreoathetosis, myoclonus and telangiectasia of eyes. Sequence analysis of ATM revealed two known nonsense mutations c.8287C > T and c.9139C > T in the siblings. Though the siblings carried the same mutations, they showed different clinical features involving strephenopodia, exotropia, torsion dystonia, myoclonus and extrapyramidal impairments. The other patient was compound heterozygotes for ATM: c.8911C > T and c.7141_7151delAATGGAAAAAT, both of which were not reported previously and not found in 200 control chromosomes. This study widens the spectrum of mutations and phenotypes in ataxia telangiectasia.