A Novel MYOC Mutation In A Chinese Family Of Juvenile-onset Open-angle Glaucoma

Purpose:1. To obtain clinical information，digital archives and DNA specimen of aChinese family with Juvenile-Onset open-angle glaucoma (JOAG).2. To describe the clinical phenotype and genetic characteristic of this JOAGpatients in the family.3. To identify the disease causing mutations of the JOAG cohort.Subjects and methods:1. Collecting and preserving clinical resources of the family including signinginformed consents, filling out JOAG questionnaire and drawing the pedigree chart.All subjects underwent comprehensive ophthalmologic examinations including bestcorrected visual acuity, intraocular pressure (IOP) teset, gonioscopy examination,central cornea thickness(CCT) test, slit lamp examination, fundus examination, visualfield test and OCT test of macular and optic nerve.2. Polymeasreehaineraction (PCR) and Sanger sequencing were implemented toscreen all the exons of the four candidate genes (CYP1B1, MYOC, OPTN andWDR36). Theresults were compared with the NCBI dbSNP database, the one thousand genomeproject and the ensemble database. Subsequently, candidate mutations were validatedin those unaffected family members and100normal individuals.Results：1. The electronic records of clinical database and blood samples database ofGD-JY001family was scientifically and normatively established in accordance withthe genetic resources collection principle.2. This cohort is consisted of14members from four generations, among whom12survived. Five affected members were diagnosed as JOAG, with the average disease onset age being14.4years (range,11-16) and the average IOP being44.2mmHg (range,28-60). Asymmetric changes of the optic nerve and visual fieldimpairment were observed. Gonioscopy showed abnormal streacture of the anteriorangle including increased pigmentation as well as bulky iris roots on trabecularmeshwork. Thinner central cornea thickness (CCT) were observed in most affectedmembers, with the average value being488.625mm (529-446mm).3. A heterozygous missense mutation c.733T＞G (p.Cys245Gly) in exon3ofMYOC has been detected in all members affected with JOAG in this GD-JY001family. This muation was found to cosegerate with the phenotype of this cohort, andwas detected absent in100unrelated normal controls. Additionally, no recordsconcerning this mutation were found in the NCBI dbSNP, the one thousand genomeproject, the ensemble database and the www.myocilin.com. No pathogenic mutationswere detedcted by sequencing of the exons of CYP1B1, OPTN and WDR36.Conclusion：1. The inheritance pattern of the GD-JY001family fits the autosomal inheritancetrait. Affected members present with early onset, predominant elevation of IOP,asymmetric impairment of the optic nerves in accordance with the loss of visual fieds.Abnormal anterior angle changes were observed in all patients, including theincreasing amounts of pigmentation and the abnormal bulky iris roots that adhere tothe angle.2. The pathogenic mutation was the heterozygous missense mutation c.733T＞G，p.Cys245Gly. Other candidate genes as CYP1B1, OPTN and WDR36had norelation to the pathogenesis of JOAG in this family.