Genetic Investigation And WDR36 Gene Mutation Of A Familial Primary Open-Angle Glaucoma In Jiangxi Province

Purpose: To research the clinical features and inheritance mode of a familial primary open-angle glaucoma (POAG) of Jiangxi province; To detect whether there is mutation of WDR36 gene and further investigate the potential role of WDR36 gene in this family.Methods: The research was approved by the ethics committee and adhered to the Helsinki Declaration. The case histories of the proband and other members were collected. Ophthalmological examinations were carried out and their clinical features were summarized; According to the acquired information, we drew the pedigree chart and then analyzed the inheritance mode of this family. The alive patients were classified in group A and other family members in group B. Group C consist of 20 healthy individuals. Their genomic DNAs were extracted from peripheral blood lymphocytes or hair follicle. All 23 exons of WDR36 gene were amplified by touch-down polymerase chain reaction (PCR).PCR fragments were sequenced to detect mutations. The significance of association of mutation frequencies were analyzed byχ2 test with bonferroni correction. We established that the difference has statistics significance when P value is less than 0.0167.Result: This pedigrees consisted of 22 individuals through 4 generations: 14 males; 8 males.8 individuals including 4 males and 4 females were diagnosed POAG, in whom 2 individuals died. The final diagnosis ages were 13～35 years old. The damages of visual field at diagnosis were at early stage and the highest intraocular pressures were 25.81-38.80 mmHg. The examinations in follow-up showed that the damage of visual field did not aggravate and the intraocular pressure maintained in normal range. The family had following inheritance characteristic:①The pedigree had four generations and there existed POAG patients in each generation;②One of the patient's parents suffered from POAG definitely;③If the parents did not suffer from POAG, their children would not suffer from the disease too;④the opportunity with disease for males and females was equal. Six mutations including four reported mutations ( Tyr216Pro,Ile264Val,Ala449Thr,Val727Val ) and two new mutations (Pro381Pro,Gly549Arg)were identified. The differences of mutation frequencies of Pro381Pro,Val727Val,Tyr216Pro,Ile264Val had not statistics significance(P>0.0167). Ala449Thr was only detected in two patients of group A. The differences of mutation frequency in Group A and C had statistics significance(P<0.0167). Gly549Arg was detected in two patients of group A and three patients of group B while not detected in Group C, The differences of mutation frequency in Group A and C had statistics significance(P<0.0167)while in Group B and C had not statistics significance(P>0.0167).Conclusion: The inheritance pattern of this family is autosomal dominant. The research suggests that WDR36 gene is related disease-causing gene of this familial POAG. The mutations of WDR36 alone are not sufficient to cause POAG; WDR36 may be a modifier gene of other disease-causing gene.