ADAMTS18基因新突变致发育性青光眼伴小角膜1家系  

A family with developmental glaucoma and microcornea due to novel ADAMTS18 gene mutations

作　　者：刘旭阳 陶宇菲 毛禹凯 陈子杰 王云[2] 洪燕芬 樊宁[2] Liu Xuyang;Tao Yufei;Mao Yukai;Chen Zijie;Wang Yun;Hong Yanfen;Fan Ning(Xiamen Eye Center of Xiamen University,Fujian Provincial Key Laboratory of Ocular Surface&Corneal Diseases,Xiamen Municipal Key Laboratory of Ocular Surface&Corneal Diseases,Xiamen Municipal Key Laboratory of Ocular Diseases,Xiamen Clinical Research Center for Eye Diseases,Xiamen 361002,China;Shenzhen Eye Hospital,the Second Clinical Medical College,Jinan University,Shenzhen 518000,China;School of Medical Technology and Engineering,Fujian Medical University,Fuzhou 350000,China)

机构地区：[1]厦门大学附属厦门眼科中心、福建省眼表与角膜病重点实验室、厦门市眼表与角膜疾病重点实验室、厦门市眼部疾病重点实验室、厦门市眼部疾病临床医学研究中心,厦门361002 [2]深圳市眼科医院、暨南大学第二临床医学院,深圳518000 [3]福建医科大学医学技术与工程学院,福州350000

出　　处：《中华眼科杂志》2024年第1期78-83,共6页Chinese Journal of Ophthalmology

基　　金：国家自然科学基金项目(82271087,82070963);广东省基础与应用基础研究基金项目(2019A1515011234);深圳市科创委基础研究项目(JCYJ20190807153005579)。

摘　　要：先证者为5岁双胞胎之胞弟,体检发现双眼眼压高1个月余,双眼眼压峰值均达25 mmHg(1 mmHg=0.133 kPa)左右,角膜横径<10 mm,眼底视杯与视盘直径比(杯盘比)扩大,相干光层析成像术(OCT)显示视网膜神经纤维层和节细胞层变薄,超声活体显微镜结合房角镜检查提示部分房角关闭,前房角发育异常。胞兄眼部表现与胞弟一致。临床诊断为双眼发育性青光眼伴小角膜。经基因测序检出双胞胎同时携带有ADAMTS18基因的2个新复合杂合突变,即M1(变异位点1):c.3436C>T:p.R1146W和M2(变异位点2):c.1454T>G:p.F485C;家系另外4名成员眼部检查正常,基因检测发现双胞胎父亲及姐姐携带M1,双胞胎母亲及哥哥携带M2。This case report presents a family with developmental glaucoma accompanied by microcornea resulting from novel mutations in the ADAMTS18 gene.The index case involves a 5-year-old twin brother,who,during a routine examination,exhibited elevated intraocular pressure persisting for over a month.The peak intraocular pressure reached approximately 25 mmHg(1 mmHg=0.133 kPa)in both eyes,with a corneal diameter of less than 10 mm.Ocular examination revealed an enlarged cup-to-disc ratio,and optical coherence tomography(OCT)demonstrated thinning of the retinal nerve fiber layer and ganglion cell layer.Ultrasound biomicroscopy combined with gonioscopy indicated partial angle closure and abnormal anterior chamber angle development.The ocular manifestations in the twin brother were consistent with those observed in the twin sister.The clinical diagnosis was bilateral developmental glaucoma with microcornea.Genetic sequencing identified two novel compound heterozygous mutations in the ADAMTS18 gene in the twins:Mutation 1(M1)involving the variant site 1(c.3436C>T:p.R1146W)and Mutation 2(M2)involving the variant site 2(c.1454T>G:p.F485C).Ocular examinations of four additional family members were normal.Genetic testing revealed that the twins′father and sister carried M1,while the index case′s mother and brother carried M2.This report underscores a unique association between ADAMTS18 gene mutations and developmental glaucoma with microcornea within a familial context,emphasizing the importance of genetic screening for early diagnosis and targeted management strategies.

关 键 词：青光眼 角膜疾病 ADAMTS蛋白质类 突变 系谱 

分 类 号：R775[医药卫生—眼科]