YAP1基因新发致病性变异致孤立性眼组织缺损一家系  

Isolated ocular colobomas caused by a novel variant of the YAP1 gene

作　　者：李杰 郭晓红 邢亚斯 路小楠 戴淑真 Li Jie;Guo Xiaohong;Xing Yasi;Lu Xiaonan;Dai Shuzhen(Henan Provincial People's Hospital,People's Hospital of Zhengzhou University,Henan Eye Hospital,Henan Eye Institute,Zhengzhou,Henan 450003,China)

机构地区：[1]河南省人民医院眼科、郑州大学人民医院眼科、河南省立眼科医院、河南省眼科研究所,郑州450003

出　　处：《中华眼底病杂志》2023年第7期544-548,共5页Chinese Journal of Ocular Fundus Diseases

基　　金：河南省医学科技攻关计划(联合共建)项目(LHGJ20200069);河南省眼科学与视觉科学重点实验室-国家临床重点专科建设项目。

摘　　要：目的确定并观察1个孤立性眼组织缺损(MAC)家系的致病基因变异与临床表型特征。方法回顾性研究。2019年5月至2022年5月于河南省立眼科医院就诊的MAC一家系1例患者和3名家系成员纳入研究。详细询问患者病史和家族史,并行最佳矫正视力(BCVA)、裂隙灯显微镜、超广角眼底彩色照相、光相干断层扫描(OCT)、B型超声检查以及眼轴长度(AL)测量。采集先证者及其父母、兄长的外周静脉血行Trio全外显子组测序,进行致病基因筛查;荧光定量聚合酶链反应验证相关变异。同时观察患者眼部及全身临床特征。结果先证者男,首次就诊时3岁。双眼眼球水平钟摆样震颤。竖椭圆形小角膜(水平直径约8.0 mm);虹膜下方缺损,呈"锁孔"状。首次就诊时(3岁)屈光度:右眼-4.00 DS/-0.50 DC×105°,左眼-3.50 DS/-1.25 DC×80°;随访3年后(6岁)屈光度及BCVA:右眼-6.50 DS/-2.00 DC×110°→0.05,左眼-6.00 DS/-1.50 DC×80°→0.2。AL:4岁10个月,右眼、左眼分别为24.62、23.92 mm;5岁7个月,右眼、左眼分别为25.24、24.36 mm.B型超声检查,双眼眼球组织缺损。超广角眼底彩色照相检查,包括视盘的下方脉络膜广泛缺损。OCT检查,双眼视盘形态结构异常,周围可见片状脉络膜缺损,缺损区神经上皮结构紊乱、变薄;左眼可见神经上皮劈裂。先证者父母及兄长表型正常。全外显子组测序结果显示,先证者YAP1基因6~9号外显子存在一个新的杂合缺失变异:YAP1,chr11:102080247-102100671,NM_001130145,loss1(EXON:6-9);生物信息学分析结果为致病变异。父母及兄长为野生型。结论发现并证实YAP1基因6~9号外显子杂合缺失为本家系的致病变异;可引起眼前节发育异常、脉络膜缺损、轴性近视加深,缺损累及黄斑与视网膜劈裂。Objective To identify the causative gene and observe the phenotypic characteristics of a family with isolated microphthalmia-anophthalmia-coloboma(MAC).Methods A retrospective clinical study.One patient(proband)and 3 family members of a family with MAC visited the Henan Eye Hospital from May 2019 to May 2022 were included in the study.The patient's medical history and family history were inquired in detail,and the best corrected visual acuity(BCVA),slit lamp microscope,fundus photography,optical coherence tomography(OCT),ophthalmological B mode ultrasound and axial length(AL)measurement were performed.The peripheral venous blood of the proband,his parents and brother was collected for Trio whole-exome sequencing and pathogenic gene screening.Fluorescence quantitative Polymerase chain reaction was used to verify the suspicious variations.The clinical features of the patient's ocular and systemic also were observed.Results The proband,male,was 3 years old at the first visit.The horizontal pendular nystagmus was detected in both eyes.Vertical elliptical microcornea and keyhole-shaped iris colobomas were detected in both eyes.The objective refraction at first visit(3 years old)was-4.00 DS/-0.50 DC×105°(OD)and-3.50 DS/-1.25 DC×80°(OS).Refraction and BCVA at 6 years old:-6.50 DS/-2.00 DC×110°→0.05(OD)and-6.00 DS/-1.50 DC×80°→0.2(OS).The AL at 4 years and 10 months old was 24.62 mm(OD)and 23.92 mm(OS),respectively.The AL at 5 years and 7 months old was 25.24 mm(OD)and 24.36 mm(OS),respectively.Ultrasonography shows tissue defects in both eyes.Fundus photography showed the inferior choroidal coloboma involving optic disc.OCT showed the optic disc in both eyes was abnormal with colobomas around,and the retinal neurosensory layer in colobomas area was disordered and thin;the retinoschisis was visible in the left eye.The proband's parents and siblings have normal phenotypes.Whole exome sequencing reveals a denovo heterozygous deletion of YAP1 gene:YAP1,chr11:10280247-102100671,NM_001130145,loss 1(EXON:6-9).The r

关 键 词：孤立性眼组织缺损 YAP1基因 基因型 表型 

分 类 号：R77[医药卫生—眼科]