背景：Usher综合征（USH）是一种常染色体隐性遗传疾病，主要导致聋盲。Usher综合征1型（USH1）亚型患者通常经历先天性感觉神经性听力损失，前庭功能异常，和视网膜色素变性（RP）。在这里，我们介绍了一例Usher综合征1F型（USH1F），在钙依赖性细胞粘附原钙粘蛋白15（PCDH15）基因中具有新的纯合变体。
方法：对眼科检查进行了为期10年的评估，并通过全外显子组测序（WES）鉴定了致病变异。10年后对彩色眼底照片的初始和随访检查显示，双眼中的骨针色素沉积增加。在眼底自发荧光（FAF）中显示出双眼的旁凹高AF环，并在8年内观察到渐进的直径方向收缩。在光谱域光学相干断层扫描（SD-OCT）上，在双眼的副凹和中央凹区域观察到外核层（ONL）丢失。全视野视网膜电图（ffERG）显示整体视网膜功能消失。WES鉴定了一个新的两碱基对缺失，c.60_61del（p.Phe21Ter),在PCDH15基因中，确认诊断为USS1F。
结论：我们报道了一种新的纯合PCDH15致病变体，预计会导致PCDH15mRNA的无义介导的衰变（NMD）。患者表现出USH1F功能丧失，经历先天性听力损失和综合征性RP。
BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene.
METHODS: Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain-optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F.
CONCLUSIONS: We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP.
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