Abstrait

Identical Ltbp2 Mutation In Poag Patients and High Risk Individual from Different Ethnic Background

Cissé Yacouba, Chen Minting, Bai Lang*, Meng Ting, Gureeye Abdirahman Abdinasir

Background: Glaucoma refers to a group of diseases characterized by atrophy of the optic nerve and visual field defects. Pathological increase of intraocular pressure is the main risk factor. Once diagnosed, glaucoma often requires immediate treatment. The purpose of treatment is the effective and timely control of elevated intraocular pressure, in order to prevent further damage to the optic nerve. However, the current various treatment measures mainly consist in reducing the intra-ocular pressure level.

Genetic factors seem to play an undeniable role in glaucoma pathogenesis; Kass and Becker were among the first to clarify the possible association between family history and glaucoma. Their initial investigations on hereditary aspects of glaucoma led to the discovery of a relationship defying simple genetic analysis. A genetic basis for glaucoma has been established through epidemiological studies, reports of large affected families, Genome-Wide Association Studies (GWAS), and animal models of glaucoma. However, the inheritance pattern of this disorder seems to be multifactorial resulting from the interaction of one or more genes and/or environmental stimuli. To date, there have multiple genetic loci and genes have been linked to POAG.

Mutations in several genes are reported to cause POAG, these genes account for less than 10% of cases worldwide. How these genes cause or influence the likelihood of developing POAG is of major interest. Genetic background (including genetic and ethnic differences) plays an important role in the pathogenesis of glaucoma, therefore, the genetic study of glaucoma pedigrees is of great significance. Targeted screening and collection of targeted genetic data for high-risk groups can provide solid evidence for clinical treatment, save patients a lot of time and money, and provide reasonable advice to undiagnosed family members in order to facilitate early detection, early diagnosis and early treatment of the condition to avoid advanced damage to the visual field.

Objectives: This study was conducted in order to investigate the role played by genetic factors in glaucoma pathogenesis through mutation screening in 3 POAG affected patients from a different ethnic background and one high-risk individual.

Methods: 1. Review and summary of relevant literature.

1. Three POAG patients from a different ethnic background and possessing both a positive family history of the condition, one high-risk individual as well as two matching ethnic background unrelated control subjects were selected for this study from the Ophthalmology Department of Nanfang Hospital. Pedigrees were drawn after inquiry of detailed family history, information on relatives, medical records and family reports. Full body characteristics (height, weight, age, sex, blood pressure, etc.) from all participants were recorded; before proceeding to conduct a complete ophthalmic examination including visual acuity, slit lamp, tonometry, goniometer, fundus (ophthalmoscopy), perimetry (visual field) and Optical Coherence Tomography (OCT).

2. Peripheral blood ( 10 ml ) was then collected from and later sent to BGI to conduct a wholeexome sequencing, with special attention given to the following glaucoma-associated genes MYOC, OPTN, WDR36, TBK1, NFT4, CYP1B1, LTBP2.

Results: No MYOC, OPTN, WDR36, TBK1, NFT4, LTBP2 and CYP1B1 mutations were detected in our study, however, the presence of LTBP2 variants was observed in the case group, comprising of 6 variants observed in subject Ai1 while 3 variants were observed in subject Ai2. The rs2196861 and rs5809669 variants are harboured by both Ai1 and Ai2. No genetic mutations were observed in the control group.

Conclusion: Glaucoma is a complex disease because genetic and environmental factors both play important roles in its pathogenesis. Our study detected novel LTBP2 gene mutations in 2 POAG patients from different ethnic backgrounds and possessing both a positive family history. The LTBP2 gene is associated with PCG, but very few studies support its role in POAG occurrence. Further investigations are needed consisting in screening large POAG families for LTBP2 mutations in order to better quantify their implication to the condition.