■CDH23的双等位基因致病变异可引起I型Usher综合征(USH1),通常以感觉神经性听力损失为特征,可变前庭反射,和渐进性的棒锥营养不良。虽然CDH23中的错义变异可导致DFNB12耳聋,其他变体可以影响钙粘蛋白23的功能,我们研究的主要目的是描述轻度色素性视网膜炎(RP)患者的基因型和表型,包括部门RP在CDH23中具有两种致病变异。
■临床检查包括病史,综合眼科检查,和多模态视网膜成像,在病例1和2中,进行全场视网膜电图(ERG)。在所有病例中都进行了遗传分析,在案例1和3中进行了先证者亲属的隔离测试。
■三个无关的病例表现为USH1的可变临床表型,并被发现在CDH23中有两个致病性变异,具有错义变异,c.5237G>A:p.Arg1746Gln是所有人的共同点。所有先证者均有轻度至重度听力损失。病例1和3有轻度RP,伴有中周边和后极保留,而案例2有部门RP。ERG结果与病例1和病例2在感光体水平下双眼视网膜功能明显丧失一致,前者峰值时间正常。
■携带c.5237G>A:CDH23中p.Arg1746Gln变体的患者可以表现为轻度表型,包括部门RP。这可以帮助更好的遗传咨询和预测。
UNASSIGNED: Biallelic pathogenic variants in CDH23 can cause Usher syndrome type I (USH1), typically characterized by sensorineural hearing loss, variable vestibular areflexia, and a progressive form of rod-cone
dystrophy. While missense variants in CDH23 can cause DFNB12 deafness, other variants can affect the cadherin 23 function, more severely causing Usher syndrome type I D. The main purpose of our study is to describe the genotypes and phenotypes of patients with mild retinitis pigmentosa (RP), including sector RP with two pathogenic variants in CDH23.
UNASSIGNED: Clinical examination included medical history, comprehensive ophthalmologic examination, and multimodal retinal imaging, and in case 1 and 2, full-field electroretinography (ERG). Genetic analysis was performed in all cases, and segregation testing of proband relatives was performed in case 1 and 3.
UNASSIGNED: Three unrelated cases presented with variable clinical phenotype for USH1 and were found to have two pathogenic variants in CDH23, with missense variant, c.5237 G > A: p.Arg1746Gln being common to all. All probands had mild to profound hearing loss. Case 1 and 3 had mild RP with mid peripheral and posterior pole sparing, while case 2 had sector RP. ERG results were consistent with the marked loss of retinal function in both eyes at the level of photoreceptor in case 1 and case 2, with normal peak time in the former.
UNASSIGNED: Patients harbouring c.5237 G > A: p.Arg1746Gln variants in CDH23 can present with a mild phenotype including sector RP. This can aid in better genetic counselling and in prognostication.