Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa.

Abstract

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.

• Authors: Nelson Chen, Hane Lee, Angela H Kim, Pei-Kang Liu, Eugene Yu-Chuan Kang, Yun-Ju Tseng, Go Hun Seo, Rin Khang, Laura Liu, Kuan-Jen Chen, We-Chi Wu, Meng-Chang Hsiao, Nan-Kai Wang
• Journal: BMC ophthalmology (BMC Ophthalmol) Vol. 22 Issue 1 Pg. 441 (Nov 16 2022) ISSN: 1471-2415 [Electronic] England
• PMID: 36384460 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Cadherins

Topics

• Humans
• Usher Syndromes (diagnosis, genetics)
• Retinitis Pigmentosa (diagnosis, genetics)
• Retina
• Cadherins (genetics)