State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China
Br J Ophthalmol. 2023 Aug;107(8):1151-1155. doi: 10.1136/bjophthalmol-2021-320084. Epub 2022 Mar 31.
BACKGROUND/AIMS: Norrin cysteine knot growth factor () located on the X chromosome, was previously reported to cause Norrie disease and familial exudative vitreoretinopathy (FEVR), which are blindness-causing ocular disorders, in males. In this study, we aimed to explore the clinical characteristics of female carriers with mutations.
Twelve female carriers from 11 unrelated families with pathogenic mutations were recruited. Clinical data were collected from the carriers. Comprehensive ocular examinations, including best corrected visual acuity, slit lamp examination, fundus photography and fundus fluorescein angiography (FFA) were evaluated. Targeted gene or whole exome sequencing was performed in the probands, and Sanger sequencing was performed to confirm mutations in female carriers.
Of the 12 females, 1 (1/12, 8.3%) presented with decreased visual acuity and 11 (11/12, 91.7%) were asymptomatic. Based on the FFA, peripheral vascular changes were noted in 66.7% (16/24) of the eyes of 75.0% (9/12) of the carriers. A total of 33.3% (8/24) had typical FEVR phenotype, 33.3% (8/24) had mild vascular abnormalities and 33.3% (8/24) was unremarkable. In addition, predominant changes such as telangiectatic endings (66.7%), anomalous circumferential vessel (37.5%), supernumerary vascular branching (33.3%), fluorescein leakage (29.2%), avascular area (8.3%), retina fold (8.3%) and peripheral straightening of retinal vessels (33.3%) were noted.
Although -related retinopathy is an X-linked recessive disorder, most of the female carriers of exhibited clinical features of FEVR. Thus, timely examinations and lifelong monitoring should be conducted in the female carriers.
背景/目的：诺里氏病胱氨酸结生长因子（Norrin）位于 X 染色体上，先前的研究报道称其突变可导致男性罹患致盲性眼病——诺里病（Norrie disease）和家族性渗出性玻璃体视网膜病变（familial exudative vitreoretinopathy，FEVR）。本研究旨在探讨携带 突变的女性携带者的临床特征。
本研究共纳入了 11 个无关家系的 12 名携带致病性 突变的女性。收集携带者的临床资料，对所有受检者进行最佳矫正视力、裂隙灯检查、眼底照相和眼底荧光素血管造影（fundus fluorescein angiography，FFA）检查。对先证者进行靶向基因或全外显子测序，对女性携带者进行 Sanger 测序以明确 突变。
12 名女性中，1 名（1/12，8.3%）视力下降，11 名（11/12，91.7%）无症状。根据 FFA 结果，24 只眼中 66.7%（16/24）存在周边血管改变，12 名携带者中有 75.0%（9/12）的眼出现典型 FEVR 表型。共有 33.3%（8/24）的眼出现典型 FEVR 表型，33.3%（8/24）的眼存在轻度血管异常，33.3%（8/24）的眼无明显异常。此外，还观察到多种病变特征，如毛细血管扩张（66.7%）、异常环形血管（37.5%）、多余血管分支（33.3%）、荧光素渗漏（29.2%）、无血管区（8.3%）、视网膜皱襞（8.3%）和视网膜周边血管变直（33.3%）。
尽管 相关性视网膜病变是一种 X 连锁隐性遗传疾病，但大多数携带 突变的女性携带者表现出 FEVR 的临床特征。因此，应对 女性携带者进行及时的检查和终生监测。
