A GLMN (glomulin) gene mutation was identified in the proband that accounts for the observed GVMs; no other family member could be tested.TIE2 sequencing revealed no mutations.
These data reveal an unexpected functional connection between Glmn and Rbx1 and demonstrate that defective regulation of Fbw7 levels contributes to GVM.
We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions.
The common mesenchymal origin of GVM and lymphatic vessels as well as the glomulin expression in vascular smooth muscle cells in utero could help explain this unusual prenatal complication of glomuvenous malformations.
We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions.
We analysed the DNA of one family with hereditary glomuvenous malformations and identified the mutation causing the disease in the glomulin gene on chromosome 1 p22.
These genes include AGGF1 for Klippel-Trenaunay syndrome, RASA1 for capillary malformations, KRIT1, MGC4607, PDCD10 for cerebral cavernous malformations, glomulin for glomuvenous malformations, TIE2 for multiple cutaneous and mucosal venous malformations, VEGFR-3, FOXC2, NEMO, SOX18 for lymphedema or related syndromes, ENG, ACVRLK1, MADH4 for HHT or related syndromes, NDP for Coats' disease, Notch3 for CADASIL, and PTEN for Proteus Syndrome.
Since all but one of the mutations result in premature stop codons, and since the localized nature of the lesions could be explained by Knudson's two-hit model, GVMs are likely caused by complete loss of function of glomulin.
Since all but one of the mutations result in premature stop codons, and since the localized nature of the lesions could be explained by Knudson's two-hit model, GVMs are likely caused by complete loss of function of glomulin.
These data reveal an unexpected functional connection between Glmn and Rbx1 and demonstrate that defective regulation of Fbw7 levels contributes to GVM.
Here, we show that Glomulin (Glmn), a protein found mutated in the vascular disorder glomuvenous malformation (GVM), binds directly to the RING domain of Rbx1 and inhibits its E3 ubiquitin ligase activity.
Here, we show that Glomulin (Glmn), a protein found mutated in the vascular disorder glomuvenous malformation (GVM), binds directly to the RING domain of Rbx1 and inhibits its E3 ubiquitin ligase activity.
Here, we show that Glomulin (Glmn), a protein found mutated in the vascular disorder glomuvenous malformation (GVM), binds directly to the RING domain of Rbx1 and inhibits its E3 ubiquitin ligase activity.