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 pr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Ophthalmology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12886-022-02659-6 |
| _version_ | 1797984106526539776 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nelson Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:57:22Z |
| format | Article |
| id | doaj.art-ff5882bf3ebc461ab4ab7b40476c4912 |
| institution | Directory Open Access Journal |
| issn | 1471-2415 |
| language | English |
| last_indexed | 2024-04-11T06:57:22Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Ophthalmology |
| spelling | doaj.art-ff5882bf3ebc461ab4ab7b40476c49122022-12-22T04:39:00ZengBMCBMC Ophthalmology1471-24152022-11-012211510.1186/s12886-022-02659-6Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosaNelson Chen0Hane Lee1Angela H. Kim2Pei-Kang Liu3Eugene Yu-Chuan Kang4Yun-Ju Tseng5Go Hun Seo6Rin Khang7Laura Liu8Kuan-Jen Chen9We-Chi Wu10Meng-Chang Hsiao11Nan-Kai Wang12Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical CenterDivision of Medical Genetics, 3billion, Inc.Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical CenterDepartment of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical CenterDepartment of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical CenterDepartment of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical CenterDivision of Medical Genetics, 3billion, Inc.Division of Medical Genetics, 3billion, Inc.Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical CenterDepartment of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical CenterDepartment of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical CenterDepartment of Pathology and Cell Biology, Columbia University Medical CenterDepartment of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical CenterAbstract 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.https://doi.org/10.1186/s12886-022-02659-6Usher syndrome type 1F (USH1F)PCDH15Protocadherin-15Loss of functionNonsense-mediated decaySyndromic retinitis pigmentosa |
| spellingShingle | 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 Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa BMC Ophthalmology Usher syndrome type 1F (USH1F) PCDH15 Protocadherin-15 Loss of function Nonsense-mediated decay Syndromic retinitis pigmentosa |
| title | Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa |
| title_full | Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa |
| title_fullStr | Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa |
| title_full_unstemmed | Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa |
| title_short | Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa |
| title_sort | case report novel pcdh15 variant causes usher syndrome type 1f with congenital hearing loss and syndromic retinitis pigmentosa |
| topic | Usher syndrome type 1F (USH1F) PCDH15 Protocadherin-15 Loss of function Nonsense-mediated decay Syndromic retinitis pigmentosa |
| url | https://doi.org/10.1186/s12886-022-02659-6 |
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