scholarly journals Atypical Ataxia Presentation in Variant Ataxia Telangiectasia: Iranian Case-Series and Review of the Literature

2022 ◽  
Vol 12 ◽  
Author(s):  
Tannaz Moeini Shad ◽  
Reza Yazdani ◽  
Parisa Amirifar ◽  
Samaneh Delavari ◽  
Marzieh Heidarzadeh Arani ◽  
...  
Keyword(s):  
T Cells ◽  
Ataxia Telangiectasia ◽  
Late Onset ◽  
Case Series ◽  
Atypical Presentation ◽  
Missense Mutations ◽  
Multisystem Disorder ◽  
Atypical Form ◽  
Increased Risk ◽  
Risk Of Cancer

Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype with an increased risk of cancer. Variant AT patients present with milder phenotype or atypical form of classical symptoms causing under- or mis- diagnosis. Although missense mutations are more frequent, an atypical presentation can be associated with deleterious mutations due to unknown modifying factors.

scholarly journals The Relationship between Pre-miR-3131 3-bp Insertion/Deletion Polymorphism and Susceptibility and Clinicopathological Characteristics of Patients with Breast Cancer

MicroRNA ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 216-223
Author(s):  
Mahsa Azizi ◽  
Nahid Rahimi ◽  
Gholamreza Bahari ◽  
Seyed Mehdi Hashemi ◽  
Mohammad Hashemi
Keyword(s):  
Breast Cancer ◽  
Case Control Study ◽  
Late Onset ◽  
Meta Analysis ◽  
Clinicopathological Characteristics ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Risk Of Cancer ◽  
The Relationship ◽  
Control Study

Aims: This study aimed at examining the effect of 3-bp pre-miR-3131 insertion/deletion (ins/del) polymorphism on Breast Cancer (BC) risk. Objectives: Totally 403 women including 199 BC patients and 204 women who have no cancer were included in this case-control study. Genotyping of miR-3131 3-bp ins/del polymorphism was performed by mismatch PCR-RFLP method. Methods: The findings expressed that the pre-miR-3131 3-bp ins/del variant was not related to the risk of BC in all genetic tested models. While, the ins/del genotype was related to late onset BC (OR=2.53, 95%CI=1.27-4.84, p=0.008). Results: Pooled results from the meta-analysis indicated to that the pre-miR-3131 ins/del is related to with an increased risk of cancer in heterozygous (OR=1.26, 95%CI=1.06-1.51, p=0.01), dominant (OR=1.33, 95%CI=1.14-1.54, p=0.0002), and allele (OR=1.24, 95%CI=1.06-1.45, p=0.006) genetics models. Conclusion: It is concluded that, our findings did not support a relationship between pre-miR-3131 ins/del polymorphism and the risk of BC. While, this variant was significantly related to late onset BC. Combined results of this study with previous studies indicated that this polymorphism increased the risk of cancer. More studies in a study with larger population with variety of ethnicities are required to verify our findings.

Ataxia-Telangiectasia genes and breast cancer risk in a French family study

2005 ◽  
Vol 72 (S1) ◽  
pp. 73-80 ◽  
Author(s):  
Nadine Andrieu ◽  
Eve Cavaciuti ◽  
Anthony Laugé ◽  
Katia Ossian ◽  
Nicolas Janin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ataxia Telangiectasia ◽  
Screening Program ◽  
Neuronal Degeneration ◽  
Carrier Status ◽  
X Rays ◽  
Increased Risk ◽  
Exogenous Factors ◽  
Atm Protein ◽  
Risk Of Cancer

Ataxia-telangiectasia (AT) is a rare autosomal recessive early childhood disorder, characterized by progressive neuronal degeneration, immunological deficiency, radiosensitivity and an increased risk of cancer caused in most cases by mutations in the AT-mutated gene (ATM). Epidemiological studies on AT families have shown that AT heterozygous women have an increased risk of developing breast cancer (BC). The ATM protein plays a central role in the recognition and repair of DNA double-strand breaks and the subsequent activation of cell-cycle checkpoints. Whilst AT is a rare disease, 0·5–1% of the general population are estimated to be AT mutation carriers, thus any increases in the risks of cancer associated with ATM carrier status are of public health relevance. The main results of our published studies on the risk of BC in 34 French AT families according to heterozygote status, type of ATM mutation and exogenous factors are summarized here. The risk of BC was higher in ATM heterozygous (HetATM) women and did not differ significantly according to the type of ATM mutation (missense vs truncating) carried by the AT family members but appeared associated with the position of some truncating mutations in certain binding domains of the ATM protein. The effect of exogenous factors, such as reproductive life factors and exposure to ionizing radiation, on the risk of BC according to ATM heterozygote status was assessed. There was no evidence for interaction (except for age at first full-term pregnancy). These findings does not appear to justify a separate screening program from that already available to other women with a first-degree relative affected by BC, as their risks have similar amplitude. Chest X-rays did not appear to be a risk factor for BC in our study population. More powerful studies, using data sets pooled from international sources are being set up to confirm these observations.

scholarly journals Rapid Flow Cytometry–Based Structural Maintenance of Chromosomes 1 (SMC1) Phosphorylation Assay for Identification of Ataxia-Telangiectasia Homozygotes and Heterozygotes

2009 ◽  
Vol 55 (3) ◽  
pp. 463-472 ◽  
Author(s):  
Shareef A Nahas ◽  
Anthony W Butch ◽  
Liutao Du ◽  
Richard A Gatti
Keyword(s):  
Flow Cytometry ◽  
Dna Damage ◽  
Ataxia Telangiectasia ◽  
Mononuclear Cells ◽  
Geometric Mean ◽  
Kinase Assay ◽  
Increased Risk ◽  
Rapid Flow ◽  
Risk Of Cancer ◽  
Structural Maintenance Of Chromosomes

Abstract Background: No rapid reliable method exists for identifying ataxia-telangiectasia (A-T) homozygotes or heterozygotes. Heterozygotes are at an increased risk of cancer and are more sensitive to the effects of ionizing radiation (IR) than the general population. We report a rapid flow cytometry (FC)-based ataxia-telangiectasia mutated (ATM) kinase assay that measures ATM- dependent phosphorylation of structural maintenance of chromosomes 1 (SMC1) following DNA damage (FC-pSMC1 assay). Methods: After optimizing conditions with lymphoblastoid cell lines (LCLs), we studied peripheral blood mononuclear cells (PBMCs) isolated from 16 healthy donors (unknowns), 10 obligate A-T heterozygotes, and 6 unrelated A-T patients. One hour after DNA damage (by either IR or bleomycin), the cells were fixed and incubated with a primary antibody to SMC1pSer966. We analyzed the stained cells by FC to determine the difference in geometric mean fluorescence intensity (ΔGMFI) of untreated and treated cells; this difference was expressed as a percentage of daily experimental controls. Results: The FC-pSMC1 assay reliably distinguished ATM heterozygotes and homozygotes from controls. Average ΔGMFI percentages (SD) of daily controls were, for unknowns, 106.1 (37.6); for A-T heterozygotes, 37.0 (18.7); and for A-T homozygotes; −8.73 (16.2). Values for heterozygotes and homozygotes were significantly different from those of controls (P < 0.0001). Conclusions: The FC-pSMC1 assay shortens the turnaround time for diagnosing A-T homozygotes from approximately 3 months to approximately 3 h. It also identifies A-T heterozygotes and can be used for prenatal counseling or for screening individuals in large study cohorts for potential ATM heterozygosity, which can then be confirmed by sequencing.

Incidence, Presentation, and Prognosis of Malignancies in Ataxia-Telangiectasia: A Report From the French National Registry of Primary Immune Deficiencies

2015 ◽  
Vol 33 (2) ◽  
pp. 202-208 ◽  
Author(s):  
Felipe Suarez ◽  
Nizar Mahlaoui ◽  
Danielle Canioni ◽  
Chantal Andriamanga ◽  
Catherine Dubois d'Enghien ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Ataxia Telangiectasia ◽  
Lymphoblastic Leukemia ◽  
Response To Treatment ◽  
Acute Leukemias ◽  
Prolymphocytic Leukemia ◽  
Increased Risk ◽  
Risk Of Cancer

Purpose Biallelic mutations in ATM cause ataxia-telangiectasia (AT), a rare inherited disease with a high incidence of cancer. Precise estimates of the risk, presentation, and outcomes of cancer in patients with AT need to be addressed in large series. Patients and Methods In this large retrospective cohort, 69 patients with cancers (24.5%) were identified among 279 patients with AT. Centralized review was performed on 60% of the lymphomas. Incidence rates were compared with the French population, and risk factors were analyzed. Results Eight patients developed acute leukemias (including four T-cell acute lymphoblastic leukemias), 12 developed Hodgkin lymphoma (HL), 38 developed non-Hodgkin lymphoma (NHL), three developed T-cell prolymphocytic leukemia (T-PLL), and eight developed carcinoma at a median age of 8.3, 10.6, 9.7, 24.2, and 31.4 years, respectively (P < .001). The majority of NHLs were aggressive B-cell NHL. Epstein-Barr virus was associated with all of the HLs and 50% of the NHLs. Overall survival was shorter in patients with AT who developed cancer compared with those who did not develop cancer (15 v 24 years, respectively; P < .001). Survival was improved in patients who achieved a major response to treatment (3.46 v 0.87 years for major v minor responses, respectively; P = .011). Immunodeficiency was associated with increased risk of cancer. ATM mutation type was associated with a difference in survival in the entire cohort but not with cancer incidence or cancer survival. Conclusion B-cell NHL, HL, and acute lymphoblastic leukemia occur at a high rate and earlier age than carcinomas in AT. T-PLLs are rarer than initially reported. Prognosis is poor, but patients may benefit from treatment with an improved survival.

Risk of Cancer by ATM Missense Mutations in the General Population

2008 ◽  
Vol 26 (18) ◽  
pp. 3057-3062 ◽  
Author(s):  
Sarah Louise Dombernowsky ◽  
Maren Weischer ◽  
Kristine Højgaard Allin ◽  
Stig Egil Bojesen ◽  
Anne Tybjjrg-Hansen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Cancer Susceptibility ◽  
Endocrine Tumors ◽  
Missense Mutations ◽  
Cancer Subtypes ◽  
Corpus Uteri ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Risk Of Cancer

Purpose Truncating and missense mutations in the ATM gene, which cause insufficient DNA damage surveillance, allow damaged cells to proceed into mitosis, which eventually results in increased cancer susceptibility. We tested the hypotheses that ATM Ser49Cys and ATM Ser707Pro heterozygosity increase the risk of cancer overall, of breast cancer, and of 26 other cancer subtypes in the general population. Patients and Methods We genotyped 10,324 individuals from the Danish general population who were observed prospectively for 36 years, during which 2,056 developed cancer. Results Multifactorially adjusted hazard ratios for ATM Ser49Cys heterozygotes versus noncarriers were 1.2 (95% CI, 0.9 to 1.5) for cancer overall, 0.8 (95% CI, 0.3 to 2.0) for breast cancer, 4.8 (95% CI, 2.2 to 11) for melanoma, 2.3 (95% CI, 1.1 to 5.0) for prostate cancer, and 3.4 (95% CI, 1.1 to 11) for cancer of the oral cavity/pharynx. Multifactorially adjusted hazard ratios for ATM Ser707Pro heterozygotes versus noncarriers were 0.8 (95% CI, 0.6 to 1.2) for cancer overall, 0.6 (95% CI, 0.2 to 1.6) for breast cancer, 10 (95% CI, 1.1 to 93) for thyroid/other endocrine tumors, and 2.7 (95% CI, 1.0 to 7.6) for cancer of corpus uteri. Conclusion ATM missense mutations do not increase the risk of cancer overall or of breast cancer in the general population; however, we observed in exploratory analyses that ATM missense mutations may be associated with an increased risk of other cancer subtypes. As we did multiple comparisons, some of these findings could represent chance findings rather than real phenomena.

scholarly journals Cancer in Children With Fanconi Anemia and Ataxia-Telangiectasia—A Nationwide Register-Based Cohort Study in Germany

2021 ◽  
Author(s):  
Christina M. Dutzmann ◽  
Claudia Spix ◽  
Isabell Popp ◽  
Melanie Kaiser ◽  
Friederike Erdmann ◽  
...  
Keyword(s):  
Dna Repair ◽  
Childhood Cancer ◽  
Hodgkin Lymphoma ◽  
Fanconi Anemia ◽  
Ataxia Telangiectasia ◽  
Population Based ◽  
Cancer Data ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Cancer In Children

PURPOSE Fanconi anemia (FA) and ataxia-telangiectasia (AT) are rare inherited syndromes characterized by abnormal DNA damage response and caused by pathogenic variants in key DNA repair proteins that are also relevant in the pathogenesis of breast cancer and other cancer types. The risk of cancer in children with these diseases is poorly understood and has never been assessed in a population-based cohort before. METHODS We identified 421 patients with FA and 160 patients with AT diagnosed between 1973 and 2020 through German DNA repair disorder reference laboratories. We linked patients' laboratory data with childhood cancer data from the German Childhood Cancer Registry. RESULTS Among 421 patients with FA, we observed 33 cases of childhood cancer (15 cases of myelodysplastic syndrome; seven cases of acute myeloid leukemia; two cases of lymphoma, carcinoma, medulloblastoma, and nephroblastoma, respectively; and one case of rhabdomyosarcoma, acute lymphoblastic leukemia, and glioma, respectively) versus 0.74 expected (on the basis of population-based incidence rates in Germany). This corresponds to a 39-fold increased risk (standardized incidence ratio [SIR] = 39; 95% CI, 26 to 56). For all FA subgroups combined, the cancer-specific SIR for myeloid neoplasms was 445 (95% CI, 272 to 687). Among the 160 patients with AT, we observed 19 cases of childhood cancer (15 cases of lymphoma, three cases of leukemia, and one case of medulloblastoma) versus 0.32 expected. This corresponds to a 56-fold increased risk (SIR = 56; 95% CI, 33 to 88). The cancer-specific SIR for Hodgkin lymphoma was 215 (95% CI, 58 to 549) and for non-Hodgkin lymphoma 470 (95% CI, 225 to 865). CONCLUSION Approximately 11% of patients with FA and 14% of patients with AT develop cancer by age 18 years.

scholarly journals ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

2015 ◽  
Vol 24 (138) ◽  
pp. 565-581 ◽  
Author(s):  
Jayesh M. Bhatt ◽  
Andrew Bush ◽  
Marjo van Gerven ◽  
Andreea Nissenkorn ◽  
Michael Renke ◽  
...  
Keyword(s):  
Lung Disease ◽  
Ataxia Telangiectasia ◽  
Causes Of Death ◽  
Respiratory Infections ◽  
Multisystem Disease ◽  
Respiratory Management ◽  
Increased Risk ◽  
Proactive Monitoring ◽  
Risk Of Cancer ◽  
Multidisciplinary Clinics

Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.

Dental Implant Placement in Patients with a History of Medications Related to Osteonecrosis of the Jaws: A Systematic Review

2020 ◽  
Author(s):  
Judd Sher ◽  
Kate Kirkham-Ali ◽  
Denny Luo ◽  
Catherine Miller ◽  
Dileep Sharma
Keyword(s):  
Systematic Review ◽  
At Risk ◽  
Drug Therapy ◽  
Dental Implant ◽  
Case Series ◽  
Cochrane Central Register ◽  
Bisphosphonate Treatment ◽  
Implant Placement ◽  
Increased Risk ◽  
History Of

The present systematic review evaluates the safety of placing dental implants in patients with a history of antiresorptive or antiangiogenic drug therapy. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and OpenGrey databases were used to search for clinical studies (English only) to July 16, 2019. Study quality was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using a modified Newcastle-Ottawa scale and the Joanna Briggs Institute critical appraisal checklist for case series. A broad search strategy resulted in the identification of 7542 studies. There were 28 studies reporting on bisphosphonates (5 cohort, 6 case control, and 17 case series) and one study reporting on denosumab (case series) that met the inclusion criteria and were included in the qualitative synthesis. The quality assessment revealed an overall moderate quality of evidence among the studies. Results demonstrated that patients with a history of bisphosphonate treatment for osteoporosis are not at increased risk of implant failure in terms of osseointegration. However, all patients with a history of bisphosphonate treatment, whether taken orally for osteoporosis or intravenously for malignancy, appear to be at risk of ‘implant surgery-triggered’ MRONJ. In contrast, the risk of MRONJ in patients treated with denosumab for osteoporosis was found to be negligible. In conclusion, general and specialist dentists should exercise caution when planning dental implant therapy in patients with a history of bisphosphonate and denosumab drug therapy. Importantly, all patients with a history of bisphosphonates are at risk of MRONJ, necessitating this to be included in the informed consent obtained prior to implant placement. The James Cook University College of Medicine and Dentistry Honours program and the Australian Dental Research Foundation Colin Cormie Grant were the primary sources of funding for this systematic review.

Neuroradiology Manifestations of Li-Fraumeni Syndrome: Epidemiology, Genetics, Imaging Findings, and Management

Neurographics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 228-235
Author(s):  
S. Naganawa ◽  
T. Donohue ◽  
A. Capizzano ◽  
Y. Ota ◽  
J. Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Soft Tissue Sarcomas ◽  
Suppressor Gene ◽  
Imaging Findings ◽  
Li Fraumeni Syndrome ◽  
Increased Risk ◽  
Li Fraumeni ◽  
Risk Of Cancer

Li-Fraumeni syndrome is a familial cancer predisposition syndrome associated with germline mutation of the tumor suppressor gene 53, which encodes the tumor suppressor p53 protein. Affected patients are predisposed to an increased risk of cancer development, including soft-tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, among other malignancies. The tumor suppressor gene TP53 plays an important, complex role in regulating the cell cycle, collaborating with transcription factors and other proteins. The disruption of appropriate cell cycle regulation by mutated TP53 is considered to be the cause of tumorigenesis in Li-Fraumeni syndrome. Appropriate surveillance, predominantly by using MR imaging, is used for early malignancy screening in an effort to improve the survival rate among individuals who are affected. Patients with Li-Fraumeni syndrome are also at increased risk for neoplasm development after radiation exposure, and, therefore, avoiding unnecessary radiation in both the diagnostic and therapeutic settings is paramount. Here, we review the epidemiology, genetics, imaging findings, and the current standard surveillance protocol for Li-Fraumeni syndrome from the National Comprehensive Cancer Network as well as potential treatment options.Learning Objective: Describe the cause of second primary malignancy among patients with Li-Fraumeni syndrome.

Case Series With Late-Onset Psychosis Hospitalized in a Geriatric Psychiatry Unit in Turkey: Experience in 9 Years

2003 ◽  
Vol 15 (1) ◽  
pp. 69-72 ◽  
Author(s):  
Yesne Alici-Evcimen ◽  
Turan Ertan ◽  
Engin Eker
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Case Series ◽  
Geriatric Psychiatry ◽  
Delusional Disorder ◽  
Early Onset Schizophrenia ◽  
Treatment Results ◽  
Thought Insertion ◽  
Psychiatry Department ◽  
Paranoid Psychosis

In this article we report the first series of Turkish inpatients with late-onset psychosis, and describe our 9-year experience at the only inpatient geriatric psychiatry department in Turkey. Among 420 patients hospitalized between 1993 and 2002, 27 were psychotic. In this group, eight patients were diagnosed as having late-onset schizophrenia (LOS) and six very-late-onset schizophrenia-like psychosis (VLOSLP). Five patients had early-onset schizophrenia and eight had delusional disorder. Females were more frequently seen in the group with LOS and the group with VLOSLP. Except for one patient with LOS, all patients with VLOSLP and LOS had paranoid psychosis. Nihilistic delusions, delusions of poverty or guilt, thought withdrawal, thought insertion, and thought broadcasting were not seen in any of the patients. Additionally, none of the LOS or VLOSLP patients showed erotomanic delusions. Grandiose and mystic delusions were not seen in those with VLOSLP. Treatment results and antipsychotic dosages at discharge were similar to those in previous reports from other cultures.

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