Abstract
Capillary malformation (CM; ‘port-wine stain’), is a common vascular malformation affecting cutaneous capillary vessels in 0.3% of newborns. Increased incidence of lesions in first-degree relatives of these patients and several reported familial cases suggest that genetic factors may play a role in the pathogenesis of CM. We report the first genome-wide linkage analysis of familial CM. In the non-parametric linkage analysis, strong evidence of linkage (peak Z-score 6.72, P-value 0.000136) was obtained in an interval of 69 cM between markers D5S407 and D5S2098, corresponding to 5q11–5q23. Parametric linkage analysis gave a maximum combined HLOD score of 4.84 (α-value 0.67) at marker D5S2044 on 5q15, and analysis using only the linked families, defined a smaller, statistically significant locus CMC1 of 23 cM (peak LOD score 7.22) between markers D5S1962 and D5S652 corresponding to 5q13–5q15. Interesting candidate genes implicated in vascular and neural development, such as MEF2C, RASA1, and THBS4, are in this locus.
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Acknowledgements
The authors are grateful to all the families involved in this study. The work was supported by the Fonds Speciaux de Recherche – Université catholique de Louvain, the Belgian Federal Service for Scientific, Technical and Cultural Affairs, and the F.N.R.S (Fonds national de la recherche scientifique) (all to M Vikkula, a ‘chercheur qualifié du F.N.R.S’). I Eerola was supported by a Marie Curie Fellowship of the European Community Program Quality of Life, under contract number QLRI-CT-1999-51491. The authors thank Ms Ana Gutierrez for technical assistance and Mrs Liliana Niculescu for secretarial help.
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Eerola, I., Boon, L., Watanabe, S. et al. Locus for susceptibility for familial capillary malformation (‘port-wine stain’) maps to 5q. Eur J Hum Genet 10, 375–380 (2002). https://doi.org/10.1038/sj.ejhg.5200817
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DOI: https://doi.org/10.1038/sj.ejhg.5200817
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