TY - JOUR T1 - A late onset variant of ataxia-telangiectasia with a compound heterozygous genotype, A8030G/7481insA JF - Journal of Medical Genetics JO - J Med Genet SP - 57 LP - 61 DO - 10.1136/jmg.39.1.57 VL - 39 IS - 1 AU - S Saviozzi AU - A Saluto AU - A M R Taylor AU - J I L Last AU - F Trebini AU - M C Paradiso AU - E Grosso AU - A Funaro AU - G Ponzio AU - N Migone AU - A Brusco Y1 - 2002/01/01 UR - http://jmg.bmj.com/content/39/1/57.abstract N2 - A taxia-telangiectasia (A-T) is a multisystem autosomal recessive disorder, with an estimated frequency of 1/40 000-1/100 000 live births.1 The ataxia-telangiectasia mutated gene (ATM), located on chromosome 11q22-23,2 encodes a nuclear 370 kDa phosphoprotein, homologous to a family of phosphatidylinositol kinase related proteins involved in DNA damage response and cell cycle regulation.3–6 Classical A-T patients show progressive cerebellar degeneration with onset in childhood, oculocutaneous telangiectasia, variable immunodeficiency, recurrent sinopulmonary infections, and high levels of serum α-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.7–9Milder cases, designated A-T variants, are a heterogeneous group characterised by a combination of one or more of the following: later onset of clinical signs, slower progression, extended life span when compared to most classical A-T patients, and decreased levels of chromosomal instability and cellular radiosensitivity.10–12 In these patients telangiectasia and/or immunodeficiency can be absent while secondary features of A-T, such as peripheral neuropathy, dysarthria, chorea and/or dystonia, are present. Cancer and recurrent sinopulmonary infections may also be absent or reduced. The genotype of A-T variants is mostly compound heterozygous for a severe mutation together with a mild or leaky mutation, which is expected to express some ATM protein with residual function.13–15A normal level of ATM protein in A-T variants can also be suggestive of mutations in other genes such as hMRE11, mutated in an A-T-like disorder with a classical A-T phenotype without telangiectasia.16–17 Other syndromes, such as Nijmegen breakage syndrome (NBS), include some A-T signs combined with a typical facies, sinopulmonary infections, … ER -