Identifying ataxia‐telangiectasia in cancer patients: Novel insights from an interesting case and review of literature

Cao, Jinyi; Tan, Ryan Ying Cong; Li, Shao-Tzu; Courtney, Eliza; Goh, Ronald Chin Hong; Fan, Bingwen Eugene; Sommat, Kiattisa; Nadarajah, Ravichandran; Ngeow, Joanne

doi:10.1002/ccr3.3543

Cited by 6 publications

(5 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the 18246 cases, family history of A-T was reported in 1274 cases ( Table 2 ) and 142 cases (53 studies) had 199 illnesses or symptoms other than A-T in a relative ( Fig 3A ). 1279 cases (109 studies [ 15 , 53 , 65 , 71 , 72 , 78 , 87 , 88 , 95 , 99 – 101 , 109 , 110 , 115 , 118 – 221 ]) were the children of consanguineous relationships, and 186 cases (86 studies [ 23 , 33 , 41 , 50 , 54 , 62 , 63 , 65 , 71 , 74 , 84 , 88 , 95 , 111 , 116 , 142 , 146 , 151 – 153 , 188 , 208 – 210 , 212 , 214 , 216 , 218 , 219 , 221 – 277 ]) were reported as being born of non-consanguineous relationships.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The natural history of ataxia-telangiectasia (A-T): A systematic review

et al. 2022

View full text Add to dashboard Cite

Background Ataxia-telangiectasia is an autosomal recessive, multi-system, and life-shortening disease caused by mutations in the ataxia-telangiectasia mutated gene. Although widely reported, there are no studies that give a comprehensive picture of this intriguing condition. Objectives Understand the natural history of ataxia-telangiectasia (A-T), as reported in scientific literature. Search methods 107 search terms were identified and divided into 17 searches. Each search was performed in PubMed, Ovid SP (MEDLINE) 1946-present, OVID EMBASE 1980 –present, Web of Science core collection, Elsevier Scopus, and Cochrane Library. Selection criteria All human studies that report any aspect of A-T. Data collection and analysis Search results were de-duplicated, data extracted (including author, publication year, country of origin, study design, population, participant characteristics, and clinical features). Quality of case-control and cohort studies was assessed by the Newcastle-Ottawa tool. Findings are reported descriptively and where possible data collated to report median (interquartile range, range) of outcomes of interest. Main results 1314 cases reported 2134 presenting symptoms. The most common presenting symptom was abnormal gait (1160 cases; 188 studies) followed by recurrent infections in classical ataxia-telangiectasia and movement disorders in variant ataxia-telangiectasia. 687 cases reported 752 causes of death among which malignancy was the most frequently reported cause. Median (IQR, range) age of death (n = 294) was 14 years 0 months (10 years 0 months to 23 years 3 months, 1 year 3 months to 76 years 0 months). Conclusions This review demonstrates the multi-system involvement in A-T, confirms that neurological symptoms are the most frequent presenting features in classical A-T but variants have diverse manifestations. We found that most individuals with A-T have life limited to teenage or early adulthood. Predominance of case reports, and case series demonstrate the lack of robust evidence to determine the natural history of A-T. We recommend population-based studies to fill this evidence gap.

show abstract

Section: Resultsmentioning

confidence: 99%

“…62 cases (27 studies [ 33 , 38 , 41 , 49 , 53 , 55 , 72 , 118 , 120 , 123 , 139 , 143 , 186 , 208 , 212 , 213 , 338 , 358 , 366 , 368 , 372 , 388 , 392 , 519 , 528 , 683 , 684 ]) reported an abnormal EMG. The youngest age at which an abnormal EMG was reported was 4 years 0 months.…”

Section: Resultsmentioning

confidence: 99%

The natural history of ataxia-telangiectasia (A-T): A systematic review

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although both c.9023G>A p.(Arg3008His) and c.1066‐6T>G variants have been described in A‐T and cancer patients, 2,6–10 the pathogenicity of c.1066‐6T>G is still debated (Table 1). This variant is relatively common in the general population 11,12 and has leaky splicing activity, 6,10 and bioinformatics tools predict it is not likely to severely affect the splice acceptor site 13 .…”

Section: Discussionmentioning

confidence: 99%

“…The association of c.9023G>A p.(Arg3008His) with a different variant (c.2304_2305insTT p.Glu769Leufs*9) was reported in a 35-year-old woman with cervical and ovarian carcinomas and sensorimotor axonal polyneuropathy. 7 She complained of walking and learning difficulties from the age of 9 and became wheelchair bound at the age of 23. Blood examination detected low immunoglobulin A and immunoglobulin G and high AFP levels.…”

Section: Discussionmentioning

confidence: 99%

Mild Neurological Phenotype Associated with Hypomorphic Variants in the Ataxia‐Telangiectasia Mutated Gene

Caputi

Federici

Soddu

et al. 2022

Movement Disord Clin Pract

View full text Add to dashboard Cite

Background Ataxia‐telangiectasia (A‐T) is a progressive multisystemic neurodegenerative disease. The phenotypic spectrum includes conditions (variant A‐T) with mild, late‐onset, and atypical clinical presentations characterized by the prevalence of dyskinetic rather than ataxic features. Cases We describe the clinical presentations of 3 siblings with early‐onset truncal ataxia without obvious neurological deterioration or biological markers of classic A‐T phenotype. We performed functional and genetic evaluation of 3 siblings with very mild neurological phenotype. Genetic evaluation with a next‐generation sequencing panel for genes causative of cerebellar ataxia detected 2 known ATM gene variants, missense c.9023G>A p.(Arg3008His), and leaky splicing c.1066‐6T>G variants. Functional studies showed mildly reduced ATM expression and residual kinase activity in the probands compared with healthy controls. Conclusions These results suggest the importance of investigating ATM variants even in the presence of clinical and biological atypical cases to ensure specific therapeutic regimens and oncological surveillance in these patients.

show abstract

“…Emerging medications that target DNA repair pathways are being tested in numerous clinical testing to treat DNA repair disorder-related cancer patients effectively while limiting side effects. The usual precautions taken to prevent direct effects include reducing radiomimetic drugs like bleomycin and dactinomycin and being aware of the potential for hemorrhagic cystitis brought on by cyclophosphamide and ifosfamide happening in patients who are prone to telangiectasias 49 . The DNA repair diseases benefit from reduced strength conditioning-based transplantation of hematopoietic stem cells due to their frequent immunosuppressive symptoms and higher risk for tumors 50 .…”

Section: Mismatch Repair (Mmr)mentioning

confidence: 99%

Role of DNA Repair Deficiency in Cancer Development

Alhegaili¹

2023

Pakistan J. of Biological Sciences

View full text Add to dashboard Cite

The DNA is constantly under attack from endogenous and exogenous damaging agents. The damaged DNA must be repaired quickly to avoid genomic instability and to prevent the occurrence of a malignant transformation. Once a lesion is detected, the DNA repair mechanism initiates and replaces the structurally altered base or any other abnormality. The cell repair mechanisms include direct reversal, excision repair (base excision repair [BER] and nucleotide excision repair [NER]), mismatch repair (MMR), homologous recombination repair (HR) and non-homologous end joining (NHEJ). Unrepaired DNA could lead to mutation, cell death or cancer. This review will discuss how the defects in DNA repair play a vital role in cancer initiation, development and progression.

show abstract

Identifying ataxia‐telangiectasia in cancer patients: Novel insights from an interesting case and review of literature

Abstract: Timely genetic testing leading to early diagnosis of A‐T is crucial due to its plethora of implications on clinical management, particularly in those who develop malignancies. Thus, clinicians have to be astute in identifying diagnostic clues of A‐T.

Cited by 6 publications

References 55 publications

The natural history of ataxia-telangiectasia (A-T): A systematic review

The natural history of ataxia-telangiectasia (A-T): A systematic review

Mild Neurological Phenotype Associated with Hypomorphic Variants in the Ataxia‐Telangiectasia Mutated Gene

Role of DNA Repair Deficiency in Cancer Development

Contact Info

Product

Resources

About