Flexibilidad laboral

We are grateful to Dr. W. Wuyts (Department of Medical Genetics, University of Antwerp, Belgium) for sending material, F. Hogervorst (department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam) for performing ATM mutation analyses and J.L. Last (department of Cancer Research UK, Institute for Cancer Studies, Birmingham University, United Kingdom) for measurements of ATM protein expression and kinase activity. We thank Evelyn de Leenheir, Edith Peeters and Linda Dewit for the technical help.

Funding: This work was supported by Stichting A-T (Gilze, the Netherlands) and by the Sheid-

NEUROPATOLOGy IN CLASSICAL AND VARIANT ATAXIA-TELANGIECTASIA

2.2

References

1. Sedgwick RP, Boder E. Ataxia telangiectasia. In Vinken PJ, Bruyn SW, de Jong JMBV, eds. Handbook of clinical neurology, vol 60: Hereditary neuropathies and spinocerebellar atrophies. New york: Elsevier Science, 1991: 347-393.

2. Savitsky K, Bar-Shira A, Gilad S, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995;268:1749-1753.

3. Taylor AM, Byrd PJ. Molecular pathology of ataxia telangiectasia. J Clin Pathol 2005;58:1009-1015.

4. Verhagen MM, Abdo WF, Willemsen MA, et al. Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology 2009;73:430-437.

5. Opeskin K, Waterston J, Nirenberg A, Hare WS. Ataxia telangiectasia with long survival. J Clin Neurosci 1998;5:471-473.

6. Navarro C, Martin JJ. Peculiar lesions in Louis-Bar ataxia-telangiectasia (in French with English summary). J Neurol Sci 1972;17:219-231.

7. Verhagen MM, van Alfen N, Pillen S, et al. Neuromuscular abnormalities in ataxia telangiectasia: a clinical, electrophysiological and muscle ultrasound study. Neuropediatrics 2007; 38:117-121.

8. Willems PJ, Van Roy BC, Kleijer WJ, Van der KM, Martin JJ. Atypical clinical presentation of ataxia telangiectasia. Am J Med Genet 1993;45:777-782.

9. Broeks A, de Klein A, Floore AN, et al. ATM germline mutations in classical ataxia-telangiectasia patients in the Dutch population. Hum Mutat 1998;12:330-337.

10. Stewart GS, Last JI, Stankovic T, et al. Residual ataxia telangiectasia mutated protein function in cells from ataxia telangiectasia patients, with 5762ins137 and 7271T-->G mutations, showing a less severe phenotype. J Biol Chem 2001;276:30133-30141.

11. Bowden DH, Danis PG, Sommers SC. Ataxia-telangiectasia. A case with lesions of ovaries and adenohypophysis. J Neuropathol Exp Neurol 1963;22:549-554.

12. Kamiya M, yamanouchi H, yoshida T, et al. Ataxia telangiectasia with vascular abnormalities in the brain parenchyma: report of an autopsy case and literature review. Pathol Int 2001;51:271-276.

13. Larnaout A, Belal S, Ben HC, Ben HM, Hentati F. Atypical ataxia telangiectasia with early childhood lower motor neuron degeneration: a clinicopathological observation in three siblings. J Neurol 1998;245:231- 235.

14. Monaco S, Nardelli E, Moretto G, Cavallaro T, Rizzuto N. Cytoskeletal pathology in ataxia-telangiectasia. Clin Neuropathol 1988;7:44-46.

15. Agamanolis DP, Greenstein JI. Ataxia-telangiectasia. Report of a case with Lewy bodies and vascular abnormalities within cerebral tissue. J Neuropathol Exp Neurol 1979;38:475-489.

16. Amromin GD, Boder E, Teplitz R. Ataxia-telangiectasia with a 32 year survival. A clinicopathological report. J Neuropathol Exp Neurol 1979;38:621-643.

17. Boder E, Sedgwick RP. Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics 1958;21:526-554.

18. Aguilar MJ, Kamoshita S, Landing BH, Boder E, Sedgwick RP. Pathological observations in ataxia-telangiectasia. A report of five cases. J Neuropathol Exp Neurol 1968;27:659-676.

19. Biemond A, van Bolhuis JH. Cerebellar atrophy with oculocutaneous telangiectasis and bronchiectasis as a familial syndrome (in Dutch with English summary). Ned Tijdschr Geneeskd 1959;103:2253-2258.

20. Centerwall SA, Centerwall WR. Ataxia-telangiectasia: a familial degenerative disease leading to mental retardation--a case report. Am J Ment Defic 1966;71:185-190.

21. Centerwall WR, Miller MM. Ataxia, telangiectasia, and sinopulmonary infections; a syndrome of slowly progressive deterioration in childhood. AMA J Dis Child 1958;95:385-396.

22. De Leon GA, Grover WD, Huff DS. Neuropathologic changes in ataxia-telangiectasia. Neurology 1976;26:947- 951.

23. Dunn HG, Meuwissen H, Livingstone CS, Pump KK. Ataxia-Telangiectasia. Can Med Assoc J 1964;91:1106- 1118.

24. Hassler O. Ataxia-telangiectasia (Louis-Bar’s syndrome). A case examined by micro-angiography with no telangiectases in the central nervous system. Acta Neurol Scand 1967;43:464-471.

25. Itatsu y, Uno y. An autopsy case of ataxia-telangiectasia. Acta Pathol Jpn 1969;19:229-239.

26. Perry TL, Kish SJ, Hinton D, Hansen S, Becker LE, Gelfand EW. Neurochemical abnormalities in a patient with ataxia-telangiectasia. Neurology 1984;34:187-191.

27. Solitare GB, Lopez VF. Louis-bar’s syndrome (ataxia-telangiectasia). Neuropathologic observations. Neurology 1967;17:23-31.

28. Sourander P, Bonnevier JO, Olsson y. A case of ataxia-telangiectasia with lesions in the spinal cord. Acta Neurol Scand 1966;42:354-366.

29. Strich SJ. Pathological Findings in 3 Cases of Ataxia-Telangiectasia. Journal of Neurology Neurosurgery and Psychiatry 1966;29:489.

30. Terplan KL, Krauss RF. Histopathologic brain changes in association with ataxia-telangiectasia. Neurology 1969;19:446-454.

31. Solitare GB. Louis-Bar’s syndrome (ataxia-telangiectasia). Anatomic considerations with emphasis on neuropathologic observations. Neurology 1968;18:1180-1186.

32. Thieffry S, Arthuis M, Farkas-Bargeton E, Vinh LT. Ataxia telangiectasia. A familial anatomo-clinical observation (in French with English summary). Ann Pediatr (Paris) 1966;13:749-762.

33. Goodman WN, Cooper WC, Kessler GB, Fischer MS, Gardner MB. Ataxia-telangiectasia. A report of two cases in siblings presenting a picture of progressive spinal muscular atrophy. Bull Los Angeles Neurol Soc 1969;34:1- 22.

34. Hiel JA, van Engelen BG, Weemaes CM, et al. Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia. Neurology 2006;67:346-349.

35. Ostetowska E, Traczynska H. Sur l’ataxia avec telangectasia, une observation anatomoclinique. On ataxia with telangiectasia, an anatomical-clinical observation (in French with English summary). Acta Neuropathol 1964;3:319-325.

36. Casaril M, Gabrielli GB, Capra F, Falezza GC. Ataxia telangiectasia. Description of a case with multiple cerebral hemorrhages and liver cirrhosis. Minerva Med 1982;73:2183-2188.

37. Gatti RA, Vinters HV. Cerebellar pathology in ataxia–telangiectasia: the significance of basket cells. In Gatti RA, Swift M, eds. Ataxia–Telangiectasia: Genetics, Neuropathology, and Immunology of a Degenerative Disease of Childhood. New york: Alan R. Liss, 1985: 225-232.

38. Vinters HV, Gatti RA, Rakic P. Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia–telangiectasia. In Gatti RA, Swift M , eds. Ataxia–Telangiectasia: Genetics, Neuropathology, and Immunology of a Degenerative Disease of Childhood. New york: Alan R. Liss, 1985: 233-255.

39. Gorodetsky E, Calkins, S, Ahn J, Brooks PJ. ATM, the Mre11/Rad50/Nbs1 complex, and topoisomerase I are concentrated in the nucleus of Purkinje neurons in the juvenile human brain. DNA Repair 2007;6:1698- 1707.

2.3 | Cognitive and speech-