THE KNOWN UK CASES OF ATAXIA TELANGIECTASIA-LIKE DISORDER (ATLD)

2015 ◽  
Vol 86 (11) ◽  
pp. e4.184-e4
Author(s):  
Katy Westwood ◽  
John Ealing ◽  
Malcolm Taylor ◽  
Paul Worth ◽  
Andrea Nemeth
Keyword(s):  
Ataxia Telangiectasia ◽  
Genome Stability ◽  
Autosomal Recessive ◽  
Atm Kinase ◽  
Clinical Presentations ◽  
Progressive Ataxia ◽  
Atm Gene ◽  
Spontaneous Chromosome ◽  
The Uk ◽  
Rare Autosomal Recessive Disease

Ataxia telangiectasia-like disorder (ATLD) is a very rare autosomal recessive disease with only 25 patients recognised worldwide. ATLD is likened to Ataxia telangiectasia (A-T) due to an overlap of clinical presentations and cellular characteristics. The clinical hallmark of A-T and ATLD is progressive young onset cerebellar ataxia. Variably present characteristics include dysarthria, oculomotor apraxia, ocular telangiectasia, immunodeficiency, spontaneous chromosome abnormalities and a predisposition to malignancy. In contrast to A-T, ocular telangiectasia is absent. Furthermore, ATLD patients tend to have a later onset and slower progression of neurological signs than A-T. The ATM gene, that has a key role in genome stability, is mutated in A-T resulting in an increase cancer predisposition. In ATLD, gene MRE11 is mutated leading to deficient activation of ATM. A functional consequence of the MRE11 mutation is raised chromosomal radiosensitivity because functional ATM kinase is required to rejoin chromosome breaks. This poster/presentation will describe the clinical features and genetic analysis of the ATLD cases with progressive ataxia known in the UK. Undergraduate Prize Winner 2015

scholarly journals Ataxia telangiectasia: what the neurologist needs to know

2020 ◽  
Vol 20 (5) ◽  
pp. 404-414
Author(s):  
May Yung Tiet ◽  
Rita Horvath ◽  
Anke E Hensiek
Keyword(s):  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Case Reports ◽  
Ataxia Telangiectasia Mutated ◽  
Systemic Complications ◽  
Atm Kinase ◽  
Clinical Presentations ◽  
Risk Of Malignancy ◽  
Delays In Diagnosis ◽  
Atypical Phenotype

Ataxia telangiectasia is an autosomal recessive DNA repair disorder characterised by complex neurological symptoms, with an elevated risk of malignancy, immunodeficiency and other systemic complications. Patients with variant ataxia telangiectasia—with some preserved ataxia telangiectasia-mutated (ATM) kinase activity—have a milder and often atypical phenotype, which can lead to long delays in diagnosis. Clinicians need to be aware of the spectrum of clinical presentations of ataxia telangiectasia, especially given the implications for malignancy surveillance and management. Here, we review the phenotypes of ataxia telangiectasia, illustrated with case reports and videos, and discuss its pathological mechanisms, diagnosis and management.

Patient with ataxia telangiectasia undergoing elective staging laparoscopy: a case report and literature review

2021 ◽  
Vol 71 (11) ◽  
pp. 2656-2658
Author(s):  
Muhammad Adeel Bashir ◽  
Huma Saleem
Keyword(s):  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Perioperative Management ◽  
Rare Condition ◽  
Staging Laparoscopy ◽  
Recurrent Infections ◽  
Ataxia Telangiectasia Mutated ◽  
Atm Gene ◽  
Autosomal Recessive Condition ◽  
Insight Into

Ataxia telangiectasia is a rare autosomal recessive condition which develops due to a mutation in the ataxia telangiectasia mutated gene (ATM gene). As a result of this mutation, the ability of the DNA to undergo repair is undermined. The resulting cellular demise is responsible for the diverse presentation of the clinical condition. Neurological symptoms such as cerebellar ataxia, abnormal eye movements and malignancies occur commonly. Immunodeficiency predisposes these patients to recurrent infections. Perioperative management of patients with this rare condition can be associated with increased morbidity. Therefore, it is recommended that patients with ataxia telangiectasia should be managed in a multidisciplinary center, under the supervision of senior clinicians who have the insight into the clinical needs of such patients. We report herein, the perioperative management of a patient with Ataxia telangiectasia undergoing laparoscopic procedure. Continuous....

scholarly journals Diagnosis and Management of Ataxia-Telangiectasia in Resource-Limited Settings

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Nienke J.H. Van Os ◽  
Koen J Van Aerde ◽  
Judith Van Gaalen ◽  
Peter J Merkus ◽  
Laura Silveira-Moriyama ◽  
...  
Keyword(s):  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Growth Failure ◽  
Autosomal Recessive Disorder ◽  
Resource Limited Settings ◽  
Diagnosis And Management ◽  
Complex Disorder ◽  
Resource Limited ◽  
Serum Alpha Fetoprotein ◽  
Atm Gene

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder linked to mutations in the ATM gene, and is characterized by neurodegeneration with an early onset cerebellar syndrome, hyperkinetic movement disorders, neuropathy, and oculocutaneous telangiectasia. Immunodeficiency, pulmonary disease, growth failure, diabetes mellitus, increased malignancy risk and hypersensitivity to ionizing radiation complicate the clinical picture. Serum alpha-fetoprotein levels are increased in patients with A-T and can therefore serve as a diagnostic marker for the disease. In resource-limited settings, diagnosis and management of patients with a rare and complex disorder such as A-T may be extremely challenging. This expert opinion-based guideline aims to give an overview of diagnosis and management of A-T in resource-limited settings, by prioritizing different options based on medical necessity, availability, and costs.

scholarly journals Case report - Ataxia-telangiectasia: innate error of immunity and neurological aspects

2021 ◽  
Author(s):  
Tarcisio Rubens da Silva ◽  
Marina Monteiro Navarro ◽  
Mylena Mendes Hóstio ◽  
Catherine Sonaly Ferreira Martins
Keyword(s):  
Case Report ◽  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Cerebellar Degeneration ◽  
Combined Immunodeficiency ◽  
Recurrent Pneumonia ◽  
Swallowing Problems ◽  
Atm Gene ◽  
Low Levels

Introduction: Among more than 350 immunological deficiencies, 25% have neurological manifestations. Thus, Ataxia-telangiectasia stands out, being considered a combined immunodeficiency. In childhood, cerebellar motor findings and recurrent sinopulmonary infections, signaling early cerebellar degeneration and deficit in the combined immune response. It has an autosomal recessive inheritance pattern. Case report: She describes herself as a female patient, 9 years old, daughter of consanguineous parents and born in Sousa, Paraíba. In the child’s neuropsychomotor development, she sat down at 5 months, verbalized loose words at 12 months and started the process of ambulation at 13 months of life. While walking, the mother noticed strange walking and frequent hospitalizations due to recurrent pneumonia. From 7 years of age, there is worsening of gait and telangiectasias in the conjunctiva are evident. Subsequently, the molecular examination in order to demonstrate the possible mutation. Therefore, a mutation described as c.7913G> A (p.Trp2638 *) was found in homozygosity in exon 53 of the ATM gene. Findings: typical onset of early childhood when walking, swallowing problems with solid and liquid foods and the growth disorder. Regarding the immune system: low levels of immunoglobulins, but without lymphopenia and the worrying presence of adenomegaly, making it necessary to always pay attention to neoplasms such as leukemias and lymphomas. In disagreement, there are no: myoclonus, the highest IgM levels, cutaneous granulomas and bone deformities. Conclusions: The case presents aspects that are very consistent with the scientific findings consolidated in Ataxia-telangiectasia, but the late molecular diagnosis.

A Novel ATM Gene Mutation Affecting Splicing in an Ataxia-Telangiectasia Patient

2021 ◽  
pp. 1-5
Author(s):  
Esra Arslan Ateş ◽  
Ayberk Türkyılmaz ◽  
Sevgi Bilgiç Eltan ◽  
Safa Barış ◽  
Ahmet Ilter Güney
Keyword(s):  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Acceptor Site ◽  
Nonsense Mediated Decay ◽  
Splicing Pattern ◽  
Progressive Ataxia ◽  
Nucleotide Insertion ◽  
Alternatively Spliced

Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, choreoathetosis and immunodeficiency beginning in early childhood. An 8-year-old girl was referred with a diagnosis of AT. She had gait disturbance and dysarthria for 3years. Multiple cutaneous telangiectases were observed on her face, trunk and limbs. Sequence analysis of the <i>ATM</i> gene revealed a homozygous c.7308–15A&#x3e;G mutation in IVS49. Human Splicing Finder predicted that the mutation could activate an intronic cryptic acceptor site. We designed primers for amplification of related exons (48–50) from cDNA for evaluating splicing pattern. Sequencing of <i>ATM</i> exons 48–50 revealed a 14-nucleotide insertion from intron 49, between exons 49 and 50, resulting in premature termination of translation at codon 2439. To conclude, we report a novel mutation in a classical AT case, which resulted in an alternatively spliced transcript and was predicted to form a truncated protein or null protein due to nonsense-mediated decay.

Ataxia-telangiectasia and combined hepatocellular-cholangiocarcinoma: A case report

2021 ◽  
Author(s):  
Tej Pratap Singh ◽  
Shraddha Patkar ◽  
Mahesh Goel ◽  
Munita Bal
Keyword(s):  
Case Report ◽  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Liver Function Tests ◽  
Radiation Sensitivity ◽  
Pulmonary Infections ◽  
Chemotherapy Dose ◽  
Combined Hepatocellular Cholangiocarcinoma ◽  
Rare Autosomal Recessive Disease

Abstract Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by ataxia, cutaneous and ocular telangiectasia, impaired immunity with susceptibility to sino-pulmonary infections, radiation sensitivity and cancers particularly of haemato-lymphoid origin. Liver function tests abnormalities and elevated alfa feto-protein have been reported in A-T however there is no reported case of combined hepatocellular-cholangiocarcinoma (cHCC-CC) in literature. These tumours should be treated in similar fashion as in general population however reduction of chemotherapy dose might be helpful in decreasing chemo-toxicity.

scholarly journals Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
D. Hettiarachchi ◽  
Hetalkumar Panchal ◽  
B. A. P. S. Pathirana ◽  
P. D. Rathnayaka ◽  
A. Padeniya ◽  
...  
Keyword(s):  
Ataxia Telangiectasia ◽  
Protein Structures ◽  
Compound Heterozygous ◽  
Sri Lankan ◽  
Gene Variants ◽  
Counseling And Testing ◽  
Whole Exome ◽  
Progressive Ataxia ◽  
Atm Gene ◽  
Atm Protein

Introduction. Ataxia telangiectasia is a rare genetic condition with an estimated prevalence of 1 in 40,000–100,000 live births. This condition predominantly affects the nervous and immune systems. It is characterized by progressive ataxia beginning from early childhood. The neurological deficit associated with this condition affects one’s balance, coordination, walking, and speech and can be accompanied by chorea, myoclonus, and neuropathy. They may also have ocular telangiectasias and high levels of blood alpha-fetoprotein (AFP). The ataxia telangiectasia mutated gene (ATM) is associated with this condition and codes for the ATM protein which is a phosphatidylinositol 3-kinase. This gene occupies 150 kb on chromosome 11q22–23 and contains 66 exons encoding a 13 kb transcript. ATM is a relatively large protein with a molecular weight of 350 kDa and 3,056 amino acids. Methods. Four patients of Sri Lankan origin presenting with features suggestive of ataxia telangiectasia were referred to our genetics center for specialized genetic counseling and testing. Whole-exome sequencing followed by Sanger sequencing was used to confirm the candidate variants. Protein modeling and genotype to phenotype correlation was performed in the identified variants. Results. We observed 6 novel ATM gene variants in four patients with ataxia telangiectasia. The identified variants are as follows: homozygous c.7397C > A (p.Ala2466Glu) and c.510_511delGT (p.Tyr171fs) and compound heterozygous c.5347_5350delGAAA (p.Glu1783fs), c.8137A > T (p.Arg2713 ∗ ) and c.1163A > C (p.Lys388Thr), and c.5227A > C (p.Thr1743Pro). Variant analysis was followed by modeling of the native and altered protein structures. Conclusion. We report novel ATM gene variants that have implications on the molecular diagnosis of ataxia telangiectasia.

Features of DNA repair in dermal fibroblasts in ataxia-telangiectasia patients with mosaic type of manifestation of active ATM kinase

2020 ◽  
Vol XV (1) ◽  
Author(s):  
M. Kuranova ◽  
A. Nozdracheva ◽  
R. Ushakov ◽  
T. Ledashcheva ◽  
L. Schugareva ◽  
...  
Keyword(s):  
Dna Repair ◽  
Ataxia Telangiectasia ◽  
Dermal Fibroblasts ◽  
Atm Kinase

scholarly journals Association of Ataxia Telangiectasia Mutated (ATM) Gene Mutation/Deletion with Rhabdomyosarcoma

2003 ◽  
Vol 2 (1) ◽  
pp. 88-92 ◽  
Author(s):  
Peilin Zhang ◽  
Kunjan S. Bhakta ◽  
Pier Lorenzo Puri ◽  
Robert Newbury ◽  
James Feramisco ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Ataxia Telangiectasia ◽  
Ataxia Telangiectasia Mutated ◽  
Atm Gene

Cerebrotendinous xanthomatosis revisited

2021 ◽  
pp. practneurol-2020-002895
Author(s):  
Seyed Mohammad Baghbanian ◽  
Mohammad Reza Mahdavi Amiri ◽  
Hadi Majidi
Keyword(s):  
Autosomal Recessive ◽  
Lipid Storage ◽  
Cerebrotendinous Xanthomatosis ◽  
Progressive Ataxia ◽  
Progressive Neurodegeneration ◽  
Prompt Diagnosis

Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid storage syndrome defined clinically by the triad of progressive neurodegeneration, juvenile cataracts and tendon xanthomas in adults. It is treatable, and a prompt diagnosis can improve outcomes. We describe a patient with this condition who presented with progressive ataxia.

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