¹Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology & Université catholique de Louvain, Brussels, Belgium

²Centre for Vascular Anomalies, Division of Plastic Surgery, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium

³Division of Plastic Surgery, Saitama Children's Medical Center, Saitama, Japan

⁴Medisud Medical Center, Brussels, Belgium

⁵Vascular Anomalies Center, Division of Plastic Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to: M Vikkula, Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology, Université catholique de Louvain, Avenue Hippocrate 74+5, bp 75.39, B-1200 Brussels, Belgium. Tel: +32 2 764 7496; Fax: +32 2 764 7548; E-mail: vikkula@bchm.ucl.ac.be

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 (-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.

European Journal of Human Genetics (2002) 10, 375-380. doi:10.1038/sj.ejhg.5200817

vascular malformation; portwine stain; linkage analysis