Title: Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1
Authors: Maertens, Ophélia ×
De Schepper, Sofie
Vandesompele, Jo
Brems, Hilde
Heyns, Ine
Janssens, Sandra
Speleman, Frank
Legius, Eric
Messiaen, Ludwine #
Issue Date: 27-Aug-2007
Series Title: American Journal of Human Genetics vol:81 issue:2 pages:243-251
Abstract: Elucidation of the biological framework underlying the development of neurofibromatosis type 1 (NF1)-related symptoms has proved to be difficult. Complicating factors include the large size of the NF1 gene, the presence of several NF1 pseudogenes, the complex interactions between cell types, and the NF1-haploinsufficient state of all cells in the body. Here, we investigate three patients with distinct NF1-associated clinical manifestations (neurofibromas only, pigmentary changes only, and association of both symptoms). For each patient, various tissues and cell types were tested with comprehensive and quantitative assays capable of detecting low-percentage NF1 mutations. This approach confirmed the biallelic NF1 inactivation in Schwann cells in neurofibromas and, for the first time, demonstrated biallelic NF1 inactivation in melanocytes in NF1-related cafe-au-lait macules. Interestingly, both disease features arise even within a background of predominantly NF1 wild-type cells. Together, the data provide molecular evidence that (1) the distinct clinical picture of the patients is due to mosaicism for the NF1 mutation and (2) the mosaic phenotype reflects the embryonic timing and, accordingly, the neural crest-derived cell type involved in the somatic NF1 mutation. The study of the affected cell types provides important insight into developmental concepts underlying particular NF1-related disease features and opens avenues for improved diagnosis and genetic counseling of individuals with mosaic NF1.
ISSN: 0002-9297
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Molecular Genetics Section (-)
Laboratory for Neurofibromatosis Research
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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