Revencu N, Boon L M, Dompmartin A, Rieu P, Busch W L, Dubois J, Forzano F, van Hagen J M, Halbach S, Kuechler A, Lachmeijer A M A, Lähde J, Russell L, Simola K O J, Mulliken J B, Vikkula M
Laboratory of Human Molecular Genetics, de Duve Institute, Brussels, Belgium ; Center for Human Genetics, Brussels, Belgium.
Mol Syndromol. 2013 Apr;4(4):173-8. doi: 10.1159/000349919. Epub 2013 Apr 11.
The RASA1 gene encodes p120RASGAP, a multidomain cytoplasmic protein that acts as a negative regulator of the RAS signalling pathway. Heterozygous loss-of-function RASA1 mutations were identified in patients with Parkes Weber syndrome and multifocal capillary malformations. This syndrome is characterised by a capillary blush on an extremity, arteriovenous microfistulas, and bony and soft tissue hypertrophy. The aim of this study was to test RASA1 in 2 disorders characterised by asymmetric limb enlargement and vascular malformations, namely Klippel-Trenaunay syndrome and regional capillary malformation with overgrowth. We did not identify any clear pathogenic change in these patients. Thus, besides clinical and radiological criteria, RASA1 testing constitutes an additional tool to differentiate Parkes Weber syndrome of capillary malformation-arteriovenous malformation (CM-AVM) from overlapping disorders.
RASA1基因编码p120RASGAP,这是一种多结构域细胞质蛋白,作为RAS信号通路的负调节因子。在患有帕克斯·韦伯综合征和多灶性毛细血管畸形的患者中发现了杂合性功能丧失性RASA1突变。该综合征的特征是肢体出现毛细血管扩张、动静脉微瘘以及骨骼和软组织肥大。本研究的目的是在两种以肢体不对称增大和血管畸形为特征的疾病中检测RASA1,即克-特综合征和伴有过度生长的局限性毛细血管畸形。我们在这些患者中未发现任何明确的致病变化。因此,除了临床和放射学标准外,RASA1检测是区分毛细血管畸形-动静脉畸形(CM-AVM)型帕克斯·韦伯综合征与重叠疾病的一种额外工具。