China
Africa
Explore chapters and articles related to this topic
Pathology and Epidemiology
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
Ataxia-telangiectasia also incorporates an important element of immunodeficiency, but is, however, more properly classified with such other conditions as Bloom’s and Fanconi’s syndromes as disorders of DNA repair. All three are inherited in an autosomal dominant fashion and may be associated with one of a number of different malignancies, notably leukemia, Hodgkin’s disease or non-Hodgkin’s lymphomas. Ataxia-telangiectasia is also exquisitely sensitive to even small doses of radiotherapy.
Phakomatoses (Neurocutaneous Syndromes)
Published in Swati Goyal, Neuroradiology, 2020
Ataxia telangiectasia Telangiectasias on the face and eye (oculocutaneous)Progressive cerebellar atrophy with ataxiaImmunodeficiency, resulting in neoplasms, and recurrent eye and sinus infections.
Ataxia Telangiectasia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Molecularly, homozygous or compound heterozygous mutation in the ATM (ataxia telangiectasia mutated) gene on chromosome 11q22.3 appears to be responsible for the pathogenesis of ataxia telangiectasia. Indeed, experimental evidence suggests that homozygous or heterozygous ATM frameshift or splice site mutations causing protein truncation are linked to classic AT, whereas ATM missense mutations that leave residual amount of functional ATM protein are implicated in mild or non-classic AT (which often presents with normal brain MRI and infrequent extraneurological features) (Table 62.1) [2].
Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients
Published in Immunological Investigations, 2021
Parisa Amirifar, Hossein Mozdarani, Reza Yazdani, Fatemeh Kiaei, Tannaz Moeini Shad, Sepideh Shahkarami, Hassan Abolhassani, Samaneh Delavari, Mahsa Sohani, Arezou Rezaei, Gholamreza Hassanpour, Seyed Mohammad Akrami, Asghar Aghamohammadi
Ataxia-telangiectasia (A-T) is a rare autosomal recessive hereditary disorder caused by germline biallelic mutations in the ataxia-telangiectasia mutated (ATM) gene, which is located at 11q22 (Chaudhary and Al-Baradie 2014; Gatti et al. 1988). The clinical features of A-T are characterized by progressive cerebellar ataxia, immunodeficiencies, oculocutaneous telangiectasia, variable immunodeficiency, recurrent sinopulmonary, radiosensitivity, and susceptibility to malignancies (Nissenkorn et al. 2016; Teive et al. 2015). Other abnormalities such as variable infections, pulmonary diseases, growth failure, insulin-resistant diabetes, gonadal atrophy, cutaneous abnormality and cardiovascular disease have been also reported in these patients (Bott et al. 2007; Nissenkorn et al. 2016; Schalch et al. 1970; Su and Swift 2000; Zaki-Dizaji et al. 2017, 2018). The incidence of this complex multisystem disorder is estimated to be between 1:40,000 to 1:300,000 live births (Swift et al. 1986).
A novel mutation in ATM gene in a Saudi female with ataxia telangiectasia
Published in International Journal of Neuroscience, 2021
Hussein Algahtani, Bader Shirah, Raghad Algahtani, Mohammad H. Al-Qahtani, Angham Abdulrahman Abdulkareem, Muhammad Imran Naseer
Ataxia telangiectasia is a hereditary multisystem disorder with a wide range of symptoms and signs [1]. It is inherited in an autosomal recessive manner due to a mutation in the ataxia telangiectasia gene (ATM), which is a large gene that extends over 184 kb and contains 66 exons producing a 13 kb mRNA [2]. The characteristics of the disease include progressive cerebellar ataxia beginning between ages one and four years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctiva, immunodeficiency with frequent infections, and an increased risk for malignancy (particularly leukemia and lymphoma) [3]. Atypical (non-classic) forms of ataxia telangiectasia include adult-onset disease and early-onset dystonia [4]. The prevalence of ataxia telangiectasia in the United States is reported to be 1:40,000-1:100,000 live births [5]. There are no epidemiological data about the incidence or prevalence of ataxia telangiectasia in Saudi Arabia. In this article, we report a novel mutation in the ATM gene in a young Saudi lady with ataxia telangiectasia. In addition, we report a few atypical features of ataxia telangiectasia in this patient and her family.
The evolution into personalized therapies in pancreatic ductal adenocarcinoma: challenges and opportunities
Published in Expert Review of Anticancer Therapy, 2018
Anteneh A. Tesfaye, Mandana Kamgar, Asfar Azmi, Philip A. Philip
Mutations in BRCA gene account for approximately 5% of all pancreatic adenocarcinomas. However, BRCA2 gene mutation account for up to 20% of all cases of familial PDAC [27]. Somatic BRCA2 mutations are also seen in sporadic cases of pancreatic adenocarcinoma. Similar in function to BRCA1, BRCA2 is involved in the repair of double-stranded breaks in DNA. Loss of BRCA2 leads to the rapid accumulation of double-strand DNA breaks and chromosomal aberrations [28]. Mutation in BRCA2 is typically seen late in tumorigenesis, probably reflecting the requisite inactivation of mediators of DNA-damage-response pathways, like TP53 [11]. Heterozygous germline mutation of PALB2 has been shown to cause a defect in DNA replication and damage response [29]. Anecdotal experience showed inactivating mutation of PALB2 gene lead to a favorable tumor response to mitomycin C treatment, as the mutation leads to disturbed BRCA1 and BRCA2 interactions and result in defective DNA double-strand break repair [30]. Ataxia telangiectasia mutated (ATM) is another gene involved in the DNA double-strand break repair [31]. In a study of 166 familial pancreatic cancer probands, 2.4% (4/166) carried deleterious ATM mutations [32]. In an integrated genomic analysis of 456 cases of pancreatic adenocarcinoma, the frequency of DNA repair genes (BRCA1, BRCA2, ATM, PALB2) mutation was 17% (5% germline and 12% somatic) [10].