Ataxia-Teleangiectasia (A-T, OMIM #208900) is a disease belonging to the group of DNA repair defects that plays an important role in the regulation of central proteins of the signaling cascade between recognition and repair of DNA damage, including the tumor suppressor proteins p53, BRCA1, CHEK2, and NBS1. A-T is characterized by increased sensitivity to ionizing radiation and progressive neurological symptoms. In the context of cancer predisposition, NHL and ALL are in the foreground.<\/p>\n<\/div>
Synonyms:<\/p>\n<\/div><\/div><\/div>
A-T<\/p>\n<\/div><\/div><\/div><\/div>
Gene:<\/p>\n<\/div><\/div><\/div>
ATM<\/em> (Ataxia telangiectasia mutated)<\/p>\n<\/div><\/div><\/div><\/div> Gen\u00ade products:<\/p>\n<\/div><\/div><\/div> Phosphatidylinsositol-3 kinase (PI3) protein family<\/p>\n<\/div><\/div><\/div><\/div> Function:<\/p>\n<\/div><\/div><\/div> ATM kinase. The pathogenic variant in ATM <\/i>leads to a down-regulation of ATM kinase expression and function, resulting in a defective DNA repair signal cascade, accumulating DNA strand breaks and genetic instability, particularly due to ionizing irradiation.<\/p>\n<\/div><\/div><\/div><\/div> Inheritance:<\/p>\n<\/div><\/div><\/div> autosomal recessive<\/p>\n<\/div><\/div><\/div><\/div> Prevalence:<\/p>\n<\/div><\/div><\/div> 1:40.000-1:100.000<\/p>\n<\/div><\/div><\/div><\/div> Genotype-phenotype correlation:<\/p>\n<\/div><\/div><\/div> c.5762-1050A>G slower neurological progression, later manifestation, intermediate radiosensitivity, low to no increased cancer risk Penetrance:<\/p>\n<\/div><\/div><\/div> High. The first neurological symptoms begin at the age of 2-4 years; by the age of 10, most children are wheelchair-bound.<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>
\nc.1A>G, c.7271T>G, c.8147T>C, c.8494C>T, etc. mild phenotype, longer survival, increased cancer risk<\/p>\n<\/div><\/div><\/div><\/div>