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Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?

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Abstract

Solitary café-au-lait spots are quite common in the general population but multiple café-au-lait macules (CALM) are often indicative of an underlying genetic disorder. The frequency of having more than five CALM is rare in normal individuals and is therefore considered as a cut-off for the diagnosis of neurofibromatosis type 1 (NF1). The etiopathogenesis of these macules is still very obscure. In this study we compared epidermal melanocyte and dermal mast cell numbers between four groups: control normal and control CALM skin, and NF1 normal and NF1 CALM skin and elaborated a possible role for stem cell factor (SCF) in CALM formation. The groups were analyzed by immunohistochemistry for numerical analysis of the melanocyte and mast cell population and by ELISA, western blot analysis and real-time quantitative PCR for further determination of the role of SCF. We found a significant increase in melanocyte density in NF1 CALM skin compared with the isolated CALM in control individuals. However, both groups displayed a similar increase in mast cell density. In addition, we found increased levels of soluble SCF in NF1 CALM and in NF1 normal fibroblast supernatant. We conclude that SCF is an important cytokine in NF1 skin, but that additional (growth) factors and/or genetic mechanisms are needed to induce NF1-specific CALM hyperpigmentation.

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Abbreviations

NF1:

neurofibromatosis type 1

SCF:

stem cell factor

CALM:

café-au-lait macule

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Acknowledgements

The authors wish to thank Martine De Mil, Sofie D’hont, Marie-Chantal Herteleer and Rita Heyse for technical assistance. Sofie De Schepper is a research fellow of the Fund for Scientific Research-Flanders, grant number G.0292.02. This work was also supported by a grant of the “Bijzonder Onderzoeksfonds” of Ghent University, grant number B/03417 (to JB) and was partially supported by the Interuniversity Attraction Poles (IUAP) grant from the Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2002–2006, P5/25, to LM).

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Authors and Affiliations

  1. Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Sofie De Schepper, Joachim Boucneau, Yves Vander Haeghen, Jean-Marie Naeyaert & Jo Lambert

  2. Department of Genetics, University of Alabama at Birmingham, 35294, AL, USA

    Ludwine Messiaen

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  1. Sofie De Schepper
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Correspondence to Jean-Marie Naeyaert.

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De Schepper, S., Boucneau, J., Vander Haeghen, Y. et al. Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?. Arch Dermatol Res 297, 439–449 (2006). https://doi.org/10.1007/s00403-006-0644-6

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