Novel Variants in <scp><i>ATM</i></scp> Causing Mild <scp>Ataxia‐Telangiectasia</scp>: From Benchside to Bedside and Back Again

Maturo, Josefina Pérez; Cid, Marcela González; Zavala, Lucía; Quiroga, Sergio Rodriguez; Kauffman, Marcelo

doi:10.1002/mdc3.13013

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…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%

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

et al. 2022

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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“…Мозочкова атаксія при синдромі Луї-Бар маніфестує зазвичай з кінця першого року життя і може бути початковим клінічним проявом хвороби [10]. Телеангіектазії на шкірі і слизових оболонках іноді бувають поодинокими, тому часто випадають з поля зору клініцистів або розвиваються пізніше, у віці 3-5 років, коли пацієнт вже тривалий час спостерігається у неврологів з приводу атаксії нез'ясованого походження або дитячого церебрального паралічу [16]. Комбінований імунодефіцит при синдромі Луї-Бар також може мати відтерміновану клінічну маніфестацію, у зв'язку з чим мозочкова атаксія нерідко є моносиндромом протягом певного часу [10].…”

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Клинический Случай Синдрома Луи-Бар С Клинической Картиной Мозжечковой Атаксии И EBV-индуцированного Лимфопролиферативного Синдрома

Maltsev¹

2021

INJ

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This description of the clinical case presents the medical history of the child aged 2 years and 6 months with a picture of Louis-Bar syndrome. Manifestations of progressive cerebellar ataxia, bruxism, oculomotor apraxia, and benign lymphoproliferative syndrome caused by Epstein-Barr virus have been reported. No signs of telangiectasia were noted, which may be explained by the age of the child. The immunological study identified signs of combined immunodeficiency with lymphopenia, a decrease in the number of T-helpers and cytotoxic T-lymphocytes in the blood, as well as low serum IgA concentration. The content of alpha-fetoprotein in the serum exceeded the normal upper limit by 15 times. Genetic test revealed three mutations in the ATM gene, in particular two known pathogenic nucleotide substitutions in the heterozygous state — c.8147T>C (p.Val2716Ala) and c.8584+2T>C (Splice donor), and one previously unknown mutation — c.3178A>G (p.fle1060Val) of uncertain diagnostic value in the heterozygous state. Valganciclovir was prescribed to inhibit reproductive activity of Epstein-Barr virus, leukocyte dialysate and propes — to compensate the immunodeficiency, and combination therapy with cerebrocurin and citicoline — for neurological deficits with a partial positive effect. This clinical example demonstrates the potential of a neuroimmunological approach to patient management, as the examined child suffered from both immunodeficiency and neurological dysfunction due to the pleiotropic effects of the mutated gene that caused the disease.

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