A late onset variant of ataxia-telangiectasia with a compound heterozygous genotype, A8030G/7481insA.

A taxia-telangiectasia (A-T) is a multisystem autosomal recessive disorder, with an estimated frequency of 1/40 000-1/100 000 live births. The ataxia-telangiectasia mutated gene (ATM), located on chromosome 11q22-23, encodes a nuclear 370 kDa phosphoprotein, homologous to a family of phosphatidylinositol kinase related proteins involved in DNA damage response and cell cycle regulation. Classical A-T patients show progressive cerebellar degeneration with onset in childhood, oculocutaneous telangiectasia, variable immunodeficiency, recurrent sinopulmonary infections, and high levels of serum -fetoprotein, chromosomal instability, and predisposition to lymphoid malignancies. The majority of patients are compound heterozygotes for two truncating ATM mutations with no detectable ATM protein. The A-T phenotype, therefore, is most commonly the result of null alleles, although missense mutations can also destabilise the protein, with similar consequences.