AB090. MOG1, the genetic modifier at 20q13, delays the age-at-onset of glaucoma by 8 to 10 years

作     者：Vincent Raymond Pascal Belleau Rose Arseneault Stéphane Dubois Jean-Louis Anctil Gilles Côté Marcel Amyot Fahed Elian Michael AWalter Québec Glaucoma Network 

作者机构：Département d’ophtalmologieCentre de rechrechr du CHU de QuébecQuébecQCCanada 

出 版 物：《Annals of Eye Science》 (眼科学年鉴（英文）)

年 卷 期：2018年第1期

页      面：496-496页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Blindness genomics complex genetic disorder gene-gene interactions biostatistics 

摘      要：Background:Primary open-angle glaucoma(POAG)is a genetically complex disorder caused primarily by gene-gene *** identify these interactions,we studied the CA family,a large French-Canadian pedigree in which the myocilin K423E mutation(MYOCK423E)causes autosomal dominant glaucoma with diagnoses ranging from juvenile-onset OAG(JOAG)to late adult-onset POAG in the heterozygotes(HTZ).To explain this extreme variability,we hypothesized that a second gene,called a modifier,was interacting with MYOC,the primary disease *** goals were(I)to map the modifier on the human genome and;(II)to characterize the symptoms affected genetically by the *** symptoms are called ***:Three hundred seventy-five CA members were studied using four quantitative endophenotypes:age of maximal intra-ocular pressures(IOPmax),IOPs progression,progression of cup to disk ratios and age-at-onset(AAO)defined as age at which ocular hypertension(OHT)was first detected with IOP≥22 ***-wide linkage analysis was performed by genotyping 408 genetic markers in 184 CA *** unbiased pedigree-based algorithm was designed to identify the individuals who were double-mutants,i.e.,these individuals carried one MYOCK423E mutation(i.e.,they were HTZ,affected or not)and they also carry simultaneously a DNA mutation within the ***:Out of the 375 CA family members investigated,156 were HTZ for the MYOCK423E mutation.120 HTZ were affected with OAG or OHT with treatment while the remaining 36 HTZ were *** ranged from 7 to 63 years old;4 individuals over 50 years old were still *** preceded optic nerve damage in98%of the HTZ carriers,confirming that AAO reflected the true severity of the *** modifier showed strong inherited effects on 2 of the 4 endophenotypes:AAO and *** next mapped with very high confidence the modifier locus for AAO at chromosome *** genotyping with additional markers refined th