ONLINE MUTATION REPORT

Automated comparative sequence analysis identifies mutations in 89% of NF1 patients and confirms a mutation cluster in exons 11–17 distinct from the GAP related domain

C Mattocks^1,2, D Baralle^1,4, P Tarpey^1,3, C ffrench-Constant^1,4, M Bobrow¹, J Whittaker¹

¹ Department of Medical Genetics, Box 134, Addenbrooke’s Hospital, Cambridge, UK
² Salisbury Reference Laboratory, UK
³ The Wellcome Trust Sanger Centre, Hinxton, UK
⁴ Department of Pathology, University of Cambridge, UK

Correspondence to:
Correspondence to:
Dr J Whittaker
Regional Genetics Laboratories, Molecular Genetics, Kefford House, Maris Lane, Trumpington, Cambridge, CB2 2FF; joanne.whittaker{at}addenbrookes.nhs.uk

Received 30 June 2003
Revised version received 20 November 2003

Accepted 21 November 2003

Keywords: comparative sequence analysis; mutation; neurofibromatosis type 1

Abbreviations: ACSA, automated comparative sequence analysis; CSA, comparative sequence analysis; GRD, GAP-related domain; NF1, neurofibromatosis type 1; NIH, National Institutes of Health

The first 150 words of the full text of this article appear below.

Neurofibromatosis type 1 (NF1), formerly known as Von Recklinghausen Neurofibromatosis, is a common genetic disorder affecting approximately 1 in 3000–5000 people. It is a fully penetrant autosomal dominant disorder. Strict diagnostic criteria that include café au lait spots, neurofibromas, plexiform neurofibromas, freckling in the axillary or inguinal regions, Lisch nodules (iris haematomas), optic or chiasma glioma, pseudoarthrosis, and sphenoid dysplasia define NF1. Most disease features are present in more than 90% of patients at puberty.¹ Further manifestations are known to occur in this disorder, including macrocephaly, short stature, learning difficulties, scoliosis and certain malignancies.^2–4 There is, however, great intra and interfamilial phenotypic variability. In addition a number of patients who have a clinical picture suspected to be NF1 do not fulfil the diagnostic criteria particularly in the younger age groups. As a consequence genetic testing would have a major impact on the diagnosis and management of these families.

The NF1 . . . [Full text of this article]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Sabbagh, A., Pasmant, E., Laurendeau, I., Parfait, B., Barbarot, S., Guillot, B., Combemale, P., Ferkal, S., Vidaud, M., Aubourg, P., Vidaud, D., Wolkenstein, P., and the members of the NF France Network, (2009). Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1. Hum Mol Genet 18: 2768-2778 [Abstract] [Full Text]  
• Ho, I. S., Hannan, F., Guo, H.-F., Hakker, I., Zhong, Y. (2007). Distinct Functional Domains of Neurofibromatosis Type 1 Regulate Immediate versus Long-Term Memory Formation. J. Neurosci. 27: 6852-6857 [Abstract] [Full Text]  
• Walker, J. A., Tchoudakova, A. V., McKenney, P. T., Brill, S., Wu, D., Cowley, G. S., Hariharan, I. K., Bernards, A. (2006). Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons. Genes Dev. 20: 3311-3323 [Abstract] [Full Text]  
• Baralle, D, Baralle, M (2005). Splicing in action: assessing disease causing sequence changes. J. Med. Genet. 42: 737-748 [Abstract] [Full Text]  
• Whittaker, J L, Mattocks, C, Baralle, D, Tarpey, P, ffrench-Constant, C, Bobrow, M (2005). Re: Pitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1 (Messiaen and Wimmer). J. Med. Genet. 42: e41-e41 [Full Text]  
• Whittaker, J L, Mattocks, C, Baralle, D, Tarpey, P, ffrench-Constant, C, Bobrow, M (2005). Re: Pitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1 (Messiaen and Wimmer). J. Med. Genet. 42: e33-e33 [Full Text]  

eLetters:

Read all eLetters

Pitfalls of comparative sequence analysis as a single platform for routine clinical testing for NF1

Ludwine M. Messiaen, et al.

J Med Genet, 14 Feb 2005 [Full text]