In our study, we have determined the ATM mutation spectrum in 19 classical A-T patients, including some immigrant populations, as well as 12 of Dutch ethnic origin.
In this report, we present the genetic characterization of a 4-year-old female with clinical diagnosis of A-T. Next-generation sequencing (NGS) revealed two novel heterozygous mutations in the ATM gene: a single-nucleotide variant (SNV) at exon 47 (NM_000051.3:c.6899G > C; p.Trp2300Ser) and ∼90 kb genomic duplication spanning exons 17-61, NG_009830.1:g.(41245_49339)_(137044_147250)dup.
Lysates of lymphoblastoid cell lines (LCLs) and peripheral blood mononuclear cells (PBMCs) from A-T patients, controls, and A-T heterozygotes were tested for ATM protein by immunoassay.
We studied 5 patients from 2 consanguineous Bedouin families of the same tribe, presenting with A-T. Whole-exome sequencing data identified the 2 aforementioned mutations in ATM, which segregated within all family members as expected of autosomal recessive heredity.
The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity.
The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis.
Zerumbone pretreatment markedly reduced ionizing radiation-induced upregulated expression of phosphorylated ATM (ataxia telangiectasia-mutated), which was partially reversed by the ATM agonist methyl methanesulfonate.
Here we show that UV-induced RPA-p34 hyperphosphorylation depends on expression of ATM, the product of the gene mutated in the human genetic disorder ataxia telangiectasia (A-T).
Ataxia-telangiectasia mutated (ATM) is the gene product mutated in ataxia-telangiectasia (A-T), which is an autosomal recessive disorder with symptoms including neurodegeneration, cancer predisposition and premature aging.
To analyze the consequences of 12 missense variants in patients with mild forms of ataxia-telangiectasia (A-T), we employed site-directed mutagenesis of ataxia-telangiectasia mutated (ATM) cDNA followed by stable transfections into a single A-T cell line to isolate the effects of each allele on the cellular phenotype.
Mutations in the ATM kinase cause the neurodegenerative disorder ataxia telangiectasia (A-T) and affected individuals are exquisitely radiation-sensitive and cancer-prone.
FLAG-ATM expression was confirmed in 293T/17 cells and human A-T fibroblasts (GM9607) after transduction, by immunoprecipitation, Western analysis, and immunocytochemistry.