Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions

Journal of Medical Genetics

Volumn 47, Issue 9, 2010, Pages 623-630

  Mautner, V F ^a   Kluwe, L ^a   Friedrich, R E ^a   Roehl, A C ^b   Bammert, S ^b   Hogel J ^b   Spori H ^b   Cooper, D N ^c   Kehrer Sawatzki, H ^b  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b UNIVERSITY OF ULM   (Germany)

^c CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

NEUROFIBROMIN;

ADOLESCENT; ARTICLE; ATTENTION DEFICIT DISORDER; BODY HEIGHT; BONE CYST; CHILD; CLINICAL ARTICLE; CLINICAL ASSESSMENT; CLINICAL FEATURE; COGNITIVE DEFECT; DISEASE ASSOCIATION; DISEASE SEVERITY; FACE DYSMORPHIA; FEMALE; FOOT; GENE; GENE DELETION; GENOTYPE PHENOTYPE CORRELATION; HAND; HUMAN; JOINT HYPERMOBILITY; LEARNING DISORDER; MALE; MENTAL DEFICIENCY; MOLECULAR GENETICS; MUSCLE HYPOTONIA; NEUROFIBROMATOSIS; NEUROPSYCHOLOGICAL TEST; NF1 GENE; PRIORITY JOURNAL; SCOLIOSIS; SPEECH DISORDER; SURVIVAL;

ADOLESCENT; BASE PAIRING; CHILD; CHILD, PRESCHOOL; CHROMOSOMES, HUMAN, PAIR 17; FACIES; FEMALE; HUMANS; MALE; NEUROFIBROMATOSIS 1; NEUROFIBROMIN 1; PHENOTYPE; SEQUENCE DELETION;

EID: 77956108381     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmg.2009.075937     Document Type: Article

References (66)

1. Kluwe L, Siebert R, Gesk S, Friedrich RE, Tinschert S, Kehrer-Sawatzki H, Mautner VF. Screening 500 unselected neurofibromatosis 1 patients for deletions of the NF1 gene. Hum Mutat 2004;23:111-16.
2. Dorschner MO, Sybert VP, Weaver M, Pletcher BA, Stephens K. NF1 microdeletion breakpoints are clustered at flanking repetitive sequences. Hum Mol Genet 2000;19:35-46.
3. Jenne DE, Tinschert S, Reimann H, Lasinger W, Thiel G, Hameister H, Kehrer-Sawatzki H. Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions. Am J Hum Genet 2001;69:516-27.
4. López-Correa C, Dorschner M, Brems H, Lázaro C, Clementi M, Upadhyaya M, Dooijes D, Moog U, Kehrer-Sawatzki H, Rutkowski JL, Fryns JP, Marynen P, Stephens K, Legius E. Recombination hotspot in NF1 microdeletion patients. Hum Mol Genet 2001;10:1387-92.
5. Forbes SH, Dorschner MO, Le R, Stephens K. Genomic context of paralogous recombination hotspots mediating recurrent NF1 region microdeletion. Genes Chromosomes Cancer 2004;41:12-25.
6. De Raedt T, Stephens M, Heyns I, Brems H, Thijs D, Messiaen L, Stephens K, Lazaro C, Wimmer K, Kehrer-Sawatzki H, Vidaud D, Kluwe L, Marynen P, Legius E. Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion. Nat Genet 2006;38:1419-23.
7. Kehrer-Sawatzki H, Kluwe L, Sandig C, Kohn M, Wimmer K, Krammer U, Peyrl A, Jenne DE, Hansmann I, Mautner VF. High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1) with microdeletions caused by somatic recombination of the JJAZ1 gene. Am J Hum Genet 2004;75:410-23.
8. Steinmann K, Cooper DN, Kluwe L, Chuzhanova NA, Senger C, Serra E, Lazaro C, Gilaberte M, Wimmer K, Mautner VF, Kehrer-Sawatzki H. Type 2 NF1 deletions are highly unusual by virtue of the absence of nonallelic homologous recombination hotspots and an apparent preference for female mitotic recombination. Am J Hum Genet 2007;81:1201-20.
9. Kehrer-Sawatzki H, Cooper DN. Mosaicism in sporadic neurofibromatosis type 1: variations on a theme common to other hereditary cancer syndromes? J Med Genet 2008;45:622-31.
10. Mantripragada KK, Thuresson AC, Piotrowski A, Díaz de Ståhl T, Menzel U, Grigelionis G, Ferner RE, Griffiths S, Bolund L, Mautner V, Nordling M, Legius E, Vetrie D, Dahl N, Messiaen L, Upadhyaya M, Bruder CE, Dumanski JP. Identification of novel deletion breakpoints bordered by segmental duplications in the NF1 locus using high resolution array-CGH. J Med Genet 2006;43:28-38.
11. Kehrer-Sawatzki H, Schmid E, Fünsterer C, Kluwe L, Mautner VF. Absence of cutaneous neurofibromas in an NF1 patient with an atypical deletion partially overlapping the common 1.4 Mb microdeleted region. Am J Med Genet A 2008;146A:691-9.
12. Pasmant E, Sabbagh A, Masliah-Planchon J, Haddad V, Hamel MJ, Laurendeau I, Soulier J, Parfait B, Wolkenstein P, Bièche I, Vidaud M, Vidaud D. Detection and characterization of NF1 microdeletions by custom high resolution array CGH. J Mol Diagn 2009;11:524-9.
13. Venturin M, Guarnieri P, Natacci F, Stabile M, Tenconi R, Clementi M, Hernandez C, Thompson P, Upadhyaya M, Larizza L, Riva P. Mental retardation and cardiovascular malformations in NF1 microdeleted patients point to candidate genes in 17q11.2. J Med Genet 2004;41:35-41.
14. Mensink KA, Ketterling RP, Flynn HC, Knudson RA, Lindor NM, Heese BA, Spinner RJ, Babovic-Vuksanovic D. Connective tissue dysplasia in five new patients with NF1 microdeletions: further expansion of phenotype and review of the literature. J Med Genet 2006;43:e8.
15. De Raedt T, Brems H, Wolkenstein P, Vidaud D, Pilotti S, Perrone F, Mautner V, Frahm S, Sciot R, Legius E. Elevated risk for MPNST in NF1 microdeletion patients. Am J Hum Genet 2003;72:1288-92.
16. Descheemaeker MJ, Roelandts K, De Raedt T, Brems H, Fryns JP, Legius E. Intelligence in individuals with a neurofibromatosis type 1 microdeletion. Am J Med Genet A 2004;131:325-6.
17. Spiegel M, Oexle K, Horn D, Windt E, Buske A, Albrecht B, Prott EC, Seemanová E, Seidel J, Rosenbaum T, Jenne D, Kehrer-Sawatzki H, Tinschert S. Childhood overgrowth in patients with common NF1 microdeletions. Eur J Hum Genet 2005;13:883-8.
18. Tonsgard JH, Yelavarthi KK, Cushner S, Short MP, Lindgren V. Do NF1 gene deletions result in a characteristic phenotype? Am J Med Genet 1997;73:80-6.
19. Wimmer K, Yao S, Claes K, Kehrer-Sawatzki H, Tinschert S, De Raedt T, Legius E, Callens T, Beiglböck H, Maertens O, Messiaen L. Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients. Genes Chromosomes Cancer 2006;5:265-76.
20. De Luca A, Bottillo I, Dasdia MC, Morella A, Lanari V, Bernardini L, Divona L, Giustini S, Sinibaldi L, Novelli A, Torrente I, Schirinzi A, Dallapiccola B. Deletions of NF1 gene and exons detected by multiplex ligation-dependent probe amplification. J Med Genet 2007;44:800-8.
21. Riccardi VM. Neurofibromatosis: phenotype, natural history and pathogenesis, 2nd edn. Baltimore: Johns Hopkins University Press, 1992:142-53.
22. Riccardi VM. Skeletal system. In: Friedman J, Gutmann D, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Baltimore: Johns Hopkins University Press, 1999:250-5.
23. Huson SM, Hughes RAC, eds. The neurofibromatosis - a pathogenetic and clinical overview. London: Chapman & Hall, 1994:169.
24. Huson SM, Harper PS, Compston DAS. Von Recklinghausen neurofibromatosis: a clinical and population study in South East Wales. Brain 1988;111:1355-81.
25. North KN. Neurofibromatosis type 1: review of the first 200 patients in an Australian clinic. J Child Neurol 1993;8:395-402.
26. Riccardi VM. Neurofibromatosis: phenotype, natural history and pathogenesis. 2nd edn. Baltimore: Johns Hopkins University Press, 1992:165-6.
27. Lewis RA, Riccardi VM. Von Recklinghausen neurofibromatosis: prevalence of iris hamartoma. Ophthalmology 1981;88:348-55.
28. Friedman JM. Evaluation and management. In: Friedman J, Gutmann D, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Baltimore: Johns Hopkins University Press, 1999:90-1.
29. Ferner RE, Hughes RA, Weinman J. Intellectual impairment in neurofibromatosis 1. J Neurol Sci 1996;138:125-33.
30. North KN, Riccardi V, Samango-Sprouse C, Ferner R, Moore B, Legius E, Ratner N, Denckla MB. Cognitive function and academic performance in neurofibromatosis. 1: consensus statement from the NF1 Cognitive Disorders Task Force. Neurology 1997;48:1121-7.
31. North KN. Cognitive function and academic performance. In: Friedman J, Gutmann D, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Baltimore: Johns Hopkins University Press, 1999:162-7.
32. Ozonoff S. Cognitive impairment in neurofibromatosis type 1. Am J Med Genet 1999;89:45-52.
33. Rosser TL, Packer RJ. Neurocognitive dysfunction in children with neurofibromatosis type 1. Curr Neurol Neurosci Rep 2003;3:129-36.
34. Hyman SL, Shores A, North KN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology 2005;65:1037-44.
35. Mautner VF, Kluwe L, Thakker SD, Leark RA. Treatment of ADHD in neurofibromatosis type 1. Dev Med Child Neurol 2002;44:164-70.
36. Riccardi VM. Skeletal system. In: Friedman J, Gutmann D, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Baltimore: Johns Hopkins University Press, 1999:262-3.
37. North K. Neurofibromatosis type 1. Am J Med Genet 2000;97:119-27.
38. Castle B, Baser ME, Huson SM, Cooper DN, Upadhyaya M. Evaluation of genotypephenotype correlations in neurofibromatosis type 1. J Med Genet 2003;40:e109.
39. Riccardi VM. Skeletal system. In: Friedman J, Gutmann D, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Baltimore: Johns Hopkins University Press, 1999:260.
40. Friedman JM. Evaluation and management. In: Friedman J, Gutmann D, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Baltimore: Johns Hopkins University Press, 1999:277-82.
41. Lin AE, Birch PH, Korf BR, Tenconi R, Niimura M, Poyhonen M, Armfield Uhas K, Sigorini M, Virdis R, Romano C, Bonioli E, Wolkenstein P, Pivnick EK, Lawrence M, Friedman JM. Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1. Am J Med Genet 2000;95:108-17.
42. Friedman JM, Arbiser J, Epstein JA, Gutmann DH, Huot SJ, Lin AE, McManus B, Korf BR. Cardiovascular disease in neurofibromatosis 1: report of the NF1 Cardiovascular Task Force. Genet Med 2002;4:105-11.
43. Tedesco MA, Di Salvo G, Natale F, Caputo S, Calabrese E, Grassia C, Ratti G, Iarussi D, Iacono A, Lama G. Cardiac abnormalities detected by Doppler imaging in patients with neurofibromatosis type 1. Am J Cardiol 2001;88:1198-200.
44. Alivuotila L, Hakokari J, Visnapuu V, Korpijaakko-Huuhka AM, Aaltonen O, Happonen RP, Peltonen S, Peltonen J. Speech characteristics in neurofibromatosis type 1. Am J Med Genet A 2010;152A:42-51.
45. Cosyns M, Vandeweghe L, Mortier G, Janssens S, Van Borsel J. Speech disorders in neurofibromatosis type 1: a sample survey. Int J Lang Commun Disord. Published Online First: 10 Nov 2009.
46. North KN. Cognitive function and academic performance. In: Friedman J, Gutmann D, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Baltimore: Johns Hopkins University Press, 1999:168.
47. Tucker T, Wolkenstein P, Revuz J, Zeller J, Friedman JM. Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology 2005;65:205-11.
48. Tonsgard JH, Kwak SM, Short MP, Dachman AH. CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform lesions. Neurology 1998;50:1755-60.
49. Waggoner DJ, Towbin J, Gottesman G, Gutmann DH. A clinic-based study of plexiform neurofibromas in neurofibromatosis 1. Am J Med Genet 2000;92:132-5.
50. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, Upadhyaya M, Towers R, Gleeson M, Steiger C, Kirby A. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 2007;44:81-8.
51. Lewis RA, Gerson LP, Axelson KA, Riccardi VM, Whitford RP. von Recklinghausen neurofibromatosis. II. Incidence of optic gliomata. Ophthalmology 1984;91:929-35.
52. Listernick R, Louis DN, Packer RJ, Gutmann DH. Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 Optic Pathway Glioma Task Force. Ann Neurol 1997;41:143-9.
53. Korf BR, Schneider G, Poussaint TY. Structural anomalies revealed by neuroimaging studies in the brains of patients with neurofibromatosis type 1 and large deletions. Genet Med 1999;1:136-40.
54. DiPaolo DP, Zimmerman RA, Rorke LB, Zackai EH, Bilaniuk LT, Yachnis AT. Neurofibromatosis type 1: pathologic substrate of high-signal-intensity foci in the brain. Radiology 1995;195:721-4.
55. Ferner RE, Chaudhuri R, Bingham J, Cox T, Hughes RA. MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry 1993;56:492-5.
56. Itoh T, Magnaldi S, White RM, Denckla MB, Hofman K, Naidu S, Bryan RN. Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. AJNR Am J Neuroradiol 1994;15:1513-19.
57. Hyman SL, Gill DS, Shores EA, Steinberg A, North KN. T2 hyperintensities in children with neurofibromatosis type 1 and their relationship to cognitive functioning. J Neurol Neurosurg Psychiatry 2007;78:1088-91.
58. Hyman SL, Gill DS, Shores EA, Steinberg A, Joy P, Gibikote SV, North KN. Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1. Neurology 2003;60:1139-45.
59. Kulkantrkorn K, Geller TJ. Seizures in neurofibromatosis type 1. Neurology 1997;48:A402.
60. Ferner RE, Gutmann DH. International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res 2002;62:1573-7.
61. Kayes LM, Riccardi VM, Burke W, Bennett RL, Stephens K. Large de novo DNA deletion in a patient with sporadic neurofibromatosis 1, mental retardation, and dysmorphism. J Med Genet 1992;29:686-90
62. Khosrotehrani K, Bastuji-Garin S, Riccardi VM, Birch P, Friedman JM, Wolkenstein P. Subcutaneous neurofibromas are associated with mortality in neurofibromatosis 1: a cohort study of 703 patients. Am J Med Genet A 2005;132A:49-53.
63. Mautner VF, Asuagbor FA, Dombi E, Fünsterer C, Kluwe L, Wenzel R, Widemann BC, Friedman JM. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol 2008;10:593-8.
64. Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 2002;39:311-14.
65. McGaughran JM, Harris DI, Donnai D, Teare D, MacLeod R, Westerbeek R, Kingston H, Super M, Harris R, Evans DG. A clinical study of type 1 neurofibromatosis in North West England. J Med Genet 1999;36:197-203.
66. Woodruff JM. Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis. Am J Med Genet 1999;89:23-30.