Clinical spectrum of ataxia-telangiectasia in adulthood
| العنوان: | Clinical spectrum of ataxia-telangiectasia in adulthood |
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| المؤلفون: | M.M.M. Verhagen, W. F. Abdo, M. A.A.P. Willemsen, F. B.L. Hogervorst, D. F.C.M. Smeets, J. A.P. Hiel, E. R. Brunt, M. A. van Rijn, D. Majoor Krakauer, R. A. Oldenburg, A. Broeks, J. I. Last, L. J. van't Veer, M. A.J. Tijssen, A. M.I. Dubois, H. P.H. Kremer, C. M.R. Weemaes, A. M.R. Taylor, M. van Deuren |
| المساهمون: | Amsterdam Neuroscience, Neurology, Pharmacy, Clinical Genetics |
| المصدر: | Neurology, 73, 6, pp. 430-7 Neurology, 73(6), 430-437. Lippincott Williams and Wilkins Neurology, 73(6), 430-437. LIPPINCOTT WILLIAMS & WILKINS Neurology, 73, 430-7 Neurology, 73(6), 430-437. Lippincott Williams & Wilkins |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, Male, EXPRESSION, Pathology, medicine.medical_specialty, VARIANT, Biology, medicine.disease_cause, PHENOTYPE, Genomic disorders and inherited multi-system disorders [IGMD 3], Ataxia Telangiectasia, Young Adult, SDG 3 - Good Health and Well-being, Chromosome instability, Genotype, medicine, KINASE, Perception and Action [DCN 1], Humans, Missense mutation, Kinase activity, Retrospective Studies, Chromosome 7 (human), Mutation, Cerebellar ataxia, Age Factors, Genetic Variation, Middle Aged, medicine.disease, ATM MUTATIONS, GENE, CANCER, GENOTYPE, 5762INS137, Pathogenesis and modulation of inflammation [N4i 1], Ataxia-telangiectasia, CELLS, Cancer research, Female, Neurology (clinical), medicine.symptom |
| الوصف: | Contains fulltext : 79696.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity. RESULTS: Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum alpha-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations. CONCLUSIONS: Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum alpha-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype. |
| وصف الملف: | application/pdf |
| تدمد: | 0028-3878 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfe0471cd48af28f57e2acfe6eec3b83Test https://doi.org/10.1212/wnl.0b013e3181af33bdTest |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....bfe0471cd48af28f57e2acfe6eec3b83 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00283878 |
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