Primary congenital glaucoma and Rieger's anomaly: extendedhaplotypes reveal founder effects for eight distinct CYP1B1mutations

[摘要] Purpose: Mutations in the cytochrome P450 1B1 (CYP1B1) gene area frequent cause of primary congenital glaucoma (PCG) in differentethnic groups. Cytochrome P450 proteins are monooxygenases, whichcatalyze many reactions involved in the metabolism of drugs as well assteroids and other lipids. The repeated occurence of several mutationsin various ethnic groups raises the question if founder effects ormutation-prone sites in CYP1B1 are the cause for this observation.Methods: A total of 30 individuals (26 PCG patients, three Rieger'sanomaly patients, and one variant carrier), presenting 17 variants inCYP1B1 (15 mutations and two variations) were included in our study.We sequenced the entire genomic region of CYP1B1 and analyzedmicrosatellites flanking the gene in all individuals and constructedhaplotypes for all variations using a combination of single nucleotidepolymorphisms and microsatellites.Results: For the CYP1B1 genomic region, we identified fiveextended haplotypes associated with 17 variations. These haplotypes werecomplemented with microsatellite information from the region surroundingthis gene. A total of eight CYP1B1 mutations were found more thanonce, each of them presenting one identical haplotype in differentindividuals. Six mutations were represented in different ethnic groups.Conclusions: Our results confirm founder effects for most ofCYP1B1 mutations. Most of these mutations must have occurred asunique events in the past.

[学科分类] 生物化学/生物物理