Here, we show that the phosphorylation observed in RPA p34 after exposure to ionizing radiation, X- or gamma-rays, is reduced and occurs later in primary fibroblasts from patients suffering from ataxia telangiectasia (AT), as compared to normal fibroblasts.
We found missense mutations of AAC (Asn) to AGC (Ser) at DCC codon 176 in one cell line and ACC (Thr) to ATC (Ile) at codon 1105 in one cell line and tumor, respectively; polymorphisms of CGA (Arg) to GGA (Gly) at codon 201 and TTT (Phe) to TTG (Leu) at codon 951 in most of the cell lines and tumors; and a silent mutation of GAG (Glu) to GAA (Glu) at codon 118 in four cell lines and five primary tumors.
Chromosomal locations of the Atm (ataxia-telangiectasia (AT)-mutated) and Acat1 (mitochondrial acetoacetyl-CoA thiolase) genes in mouse, rat, and Syrian hamster were determined by direct R-banding FISH.
We previously reported that no recombinations are found among Atm, Npat, and Acat1 (acetoacetyl-CoA thiolase) loci as determined by fine genetic linkage mapping of the mouse AT region.
We have constructed a long-range physical map for 12 markers, including genes for GRIA4, IL1BC, and ACAT, across 9 Mb of chromosome 11q22-q23 in the region of the major locus for ataxia-telangiectasia (A-T).
At the protein level, the major luminal neutral amino acid transporter B<sup>0</sup>AT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 were shown by immunofluorescence to be expressed similarly in newborns and in adults.
The results indicate that regulation of the fibronectin gene in A-T fibroblasts differs from that of the integrin and beta-actin genes, and that the decline in fibronectin mRNA may be linked to the shortened in vitro life-span of these cells.
We were the first to analyze Arg16Gly ADRB2 gene polymorphism in Japanese patients with AERD, and showed that Arg16GlyADRB2 gene polymorphism in Japanese patients with AERD is different from that in the patients with ATA.
Both mutations detected in ATM have been shown to be pathogenic, and α-fetoprotein, a marker of ataxia telangiectasia, was increased in all affected individuals.
Nineteen cases presented with non-conclusive results, mostly due to poor mitogen response; however, a combination of cell-cycle data with serum AFP concentrations led to the exclusion of AT in all but two of the uncertain cases.
In spite of many resemblances, this syndrome differs from classical or complete ataxia telangiectasia in that oculocutaneous telangiectases were lacking, the serum IgA and alpha-fetoprotein levels in this family were normal, there was no gonadal dysgenesis, and the cytogenetic findings were atypical.
In two patients with this syndrome, normal levels of serum immunoglobulins and alpha-fetoprotein, chromosomal stability in peripheral blood lymphocytes and skin fibroblasts, and normal cellular response to treatments with X-rays and the radiomimetic drug neocarzinostatin indicated that this disease does not share, with A-T, any additional features other than ataxia.
Although they all had raised serum AFP levels, their clinical, immunological, biochemical, cytogenetic and molecular genetic studies failed to support a diagnosis of Ataxia Telangiectasia.
A case of a young white female with AT who developed hepatocellular carcinoma along with significantly elevated levels of alpha fetoprotein is presented.
Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasia, immunodeficiency, elevated alpha-fetoprotein level, chromosomal instability, predisposition to cancer, and radiation sensitivity.
Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated α-fetoprotein levels.
Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis.
Testing for vitamin E (for ataxia with isolated vitamin E deficiency) and alpha fetoprotein (for Ataxia Telangiectasia or AT) are important, as is empiric treatment with coenzyme Q10 for those genetic abnormalities that can lead to coenzyme Q deficiency.
Four strains demonstrated RDS that was less pronounced than in most AT cells: one was from a patient with Nijmegen breakage syndrome, one was from a patient without ataxia but with choreiform movement disorder, telangiectasia, and elevated concentrations of alpha-fetoprotein in the blood, and two were from AT patients.