Background/Aims To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 ( PRSS56 ), membrane-type frizzled-related protein ( MFRP ), myelin regulatory factor ( MYRF ) and transmembrane protein 98 ( TMEM98 ) and to evaluate the association between angle-closure glaucoma (ACG) and NNO. Methods Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis. Results Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP . Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma. Conclusion Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling. Data are available upon reasonable request.

中文翻译：

---

纳米眼球基因突变患者的临床特征


背景/目的 区分蛋白酶丝氨酸 56 （PRSS56） 、膜型卷曲相关蛋白 （MFRP） 、髓鞘调节因子 （MYRF） 和跨膜蛋白 98 （TMEM98） 突变引起的纳米眼球 （NNO） 的临床特征，并评价闭角型青光眼 （ACG） 与 NNO 之间的关联。方法 通过外显子组测序/全基因组测序数据鉴定这 4 个基因的变异，并进行生物信息学分析以鉴定致病性/可能致病性 （P/LP） 变异。这项观察性研究全面总结了来自 67 个家庭的 63 名 NNO 患者的眼科数据。对 68 只未手术治疗的眼睛的眼部参数进行进一步分析。结果 共 63 个家系的 67 例患者在 4 个基因中携带 57 个 P/LP 变异，其中 PRSS56 30 个 （47.6%），MFRP 23 个 （36.5%），TMEM98 5 个 （7.9%） 和 MYRF 5 个 （7.9%）。79.1% 的患者存在 ACG。对 68 只眼睛的眼部参数分析显示，较短的眼轴长度 （AL）、较低的玻璃体与 AL 比率和严重的中心凹发育不全与 PRSS56 和 MFRP 的变异有关。葡萄膜积液在 PRSS56 变异患者中更常见，而视网膜色素变性在 MFRP 变异患者中常见。MYRF 变异患者表现出最薄的视网膜神经纤维层厚度。TMEM98 变异患者青光眼的平均发病年龄较早。结论 PRSS56 和 MFRP 变异是 NNO 最常见的遗传原因。ACG 是这些患者中经常观察到的严重并发症。在显性 NNO 患者中观察到 ACG 的早期发作，而中心凹发育不全在隐性疾病患者中更常见。 识别这些特征有助于临床护理和遗传咨询。数据可根据合理要求提供。