Journal
BMC OPHTHALMOLOGY
Volume 22, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12886-022-02659-6
Keywords
Usher syndrome type 1F (USH1F); PCDH15; Protocadherin-15; Loss of function; Nonsense-mediated decay; Syndromic retinitis pigmentosa; Congenital hearing loss; Case report
Categories
Funding
- National Institute of Health [R01EY031354, P30EY019007]
- Vagelos College of Physicians & Surgeons (VPS) Grants
- Gerstner Philanthropies
- Chang Gung Memorial Hospital Research Grant [CMRPG3M0631]
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This case report presents a novel homozygous variant in the PCDH15 gene in a patient with USH1F, leading to congenital hearing loss and syndromic RP. The identified pathogenic variant is expected to result in NMD of PCDH15 mRNA.
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. Case presentation 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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