A gene for familial venous malformations maps to chromosome 9p in a second large kindred.

Abstract

Methods SUBJECTSAfter obtaining informed consent, each participant (38 members of the family, fig 1) was interviewed and examined by the same physician (KAP). Physical examinations were performed and family histories were taken. Affected status was assigned on the basis of one or more venous malformations. Other vascular anomalies, such as lateral telangiectatic naevi (port wine stains), were occasionally noted but not included as part of the affected phenotype. Blood was drawn from appropriate subjects and DNA was extracted using established methods.3 GENOTYPES AND LINKAGE ANALYSISAnalyses of simple repeat markers were performed as previously described.3 The venous malformation phenotype was analysed as an autosomal dominant disorder with age dependent penetrance. For estimating the age dependent penetrance, four liability classes were created with age ranges 0-12 (penetrance 0 5), 12-21 (penetrance 0-75) 21-45 (0 90), and >45 (0-95), based on observations from more than 10 years of clinical contact with the entire extended family. Disease frequency was set at 0-0001. Two point linkage analysis was performed on a Sun Sparc station 10 using the MLINK subprogram of the LINKAGE computer package (version 4-9).4 The analysis was repeated using the phenotypic information on only the affected subjects to ensure that information was coming only from those with a definitive disease status. Allele frequency was estimated for the markers using the pedigree maximum likelihood estimation from the family data by the method of Boehnke' and did not differ appreciably from the allele frequencies listed in GDB.

Progress toward Understanding Vascular Malformations

“…Rarely familial occurrencess with multiple lesions are described (100)(101)(102) (117). Familial aggregation has been described repeatedlyy indicating autosomal dominant inheritance (117)(118)(119).…”

Blue rubber bleb naevus syndrome and chiari malformation: high risk of peroperative haemorrhage.

“…On a molecular and genetic level, the disease process leading to the clinical manifestations of BRBNS is poorly understood. Although BRBNS develops sporadically in most cases, it is sometimes inherited in an autosomal dominant pattern (chromosome 9p) (5). A locus on the same gene has also been associated with familiar venous malformations and it has been hypothesised that BRBNS may be a subset in the general category of familial venous malformations (5).…”

“…Although BRBNS develops sporadically in most cases, it is sometimes inherited in an autosomal dominant pattern (chromosome 9p) (5). A locus on the same gene has also been associated with familiar venous malformations and it has been hypothesised that BRBNS may be a subset in the general category of familial venous malformations (5). In patients with BRBNS, the c-kit (a stem cell growth factor receptor, previously described with respect to angiogenesis) was found in smallsized vessels within the specimens of a patient with BRBNS (7).…”

New Trends in Management of Epilepsy in Patients with Cerebral Venous Malformations: Our Experience

“…[27,[29][30][31] These might occasionally develop as a result of dominant inheritance of a gene mutation in the short arm of chromosome 9. [32] DVAs can either drain into deep subependymal veins and the galenic system or drain into superficial cortical veins. The superficial pattern is present in about 70%, while the deep drainage pattern is present in 20% of the population.…”