Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression
| Main Author: | |
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| Publication Date: | 2024 |
| Other Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10362/172704 |
Summary: | Publisher Copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. |
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Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expressionAfrican ancestryancestral alleleciliopathyequity of genetic testingethnic genetic diversitygene expressionnon-coding genetic variationretinal dystrophyretinitis pigmentosaSouth AsianGeneticsGenetics(clinical)Publisher Copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNMalka, SamanthaBiswas, PoojaBerry, Anne MarieSangermano, RiccardoUllah, MukhtarLin, SiyingD'Antonio, MatteoJestin, AleksandrJiao, XiaodongQuinodoz, MathieuSullivan, LoriGardner, Jessica C.Place, Emily M.Michaelides, MichelKaminska, KarolinaMahroo, Omar A.Schiff, ElenaWright, GenevieveCancellieri, FrancescaVaclavik, VeronikaSantos, CristinaRehman, Atta UrMehrotra, SudeepAzhar Baig, Hafiz MuhammadIqbal, MuhammadAnsar, MuhammadSantos, Luisa CoutinhoSousa, Ana BertaTran, Viet H.Matsui, HirokoBhatia, AnjanaNaeem, Muhammad AsifAkram, Shehla J.Akram, JavedRiazuddin, SheikhAyuso, CarmenPierce, Eric A.Hardcastle, Alison J.Riazuddin, S. AmerFrazer, Kelly A.Hejtmancik, J. FieldingRivolta, CarloBujakowska, Kinga M.Arno, GavinWebster, Andrew R.Ayyagari, Radha2024-09-30T22:28:48Z2024-09-052024-09-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article19application/pdfhttp://hdl.handle.net/10362/172704eng1537-6605PURE: 99518474https://doi.org/10.1016/j.ajhg.2024.07.020info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-02-10T01:36:43Zoai:run.unl.pt:10362/172704Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T18:55:17.953971Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression |
| title |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression |
| spellingShingle |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression Malka, Samantha African ancestry ancestral allele ciliopathy equity of genetic testing ethnic genetic diversity gene expression non-coding genetic variation retinal dystrophy retinitis pigmentosa South Asian Genetics Genetics(clinical) |
| title_short |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression |
| title_full |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression |
| title_fullStr |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression |
| title_full_unstemmed |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression |
| title_sort |
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression |
| author |
Malka, Samantha |
| author_facet |
Malka, Samantha Biswas, Pooja Berry, Anne Marie Sangermano, Riccardo Ullah, Mukhtar Lin, Siying D'Antonio, Matteo Jestin, Aleksandr Jiao, Xiaodong Quinodoz, Mathieu Sullivan, Lori Gardner, Jessica C. Place, Emily M. Michaelides, Michel Kaminska, Karolina Mahroo, Omar A. Schiff, Elena Wright, Genevieve Cancellieri, Francesca Vaclavik, Veronika Santos, Cristina Rehman, Atta Ur Mehrotra, Sudeep Azhar Baig, Hafiz Muhammad Iqbal, Muhammad Ansar, Muhammad Santos, Luisa Coutinho Sousa, Ana Berta Tran, Viet H. Matsui, Hiroko Bhatia, Anjana Naeem, Muhammad Asif Akram, Shehla J. Akram, Javed Riazuddin, Sheikh Ayuso, Carmen Pierce, Eric A. Hardcastle, Alison J. Riazuddin, S. Amer Frazer, Kelly A. Hejtmancik, J. Fielding Rivolta, Carlo Bujakowska, Kinga M. Arno, Gavin Webster, Andrew R. Ayyagari, Radha |
| author_role |
author |
| author2 |
Biswas, Pooja Berry, Anne Marie Sangermano, Riccardo Ullah, Mukhtar Lin, Siying D'Antonio, Matteo Jestin, Aleksandr Jiao, Xiaodong Quinodoz, Mathieu Sullivan, Lori Gardner, Jessica C. Place, Emily M. Michaelides, Michel Kaminska, Karolina Mahroo, Omar A. Schiff, Elena Wright, Genevieve Cancellieri, Francesca Vaclavik, Veronika Santos, Cristina Rehman, Atta Ur Mehrotra, Sudeep Azhar Baig, Hafiz Muhammad Iqbal, Muhammad Ansar, Muhammad Santos, Luisa Coutinho Sousa, Ana Berta Tran, Viet H. Matsui, Hiroko Bhatia, Anjana Naeem, Muhammad Asif Akram, Shehla J. Akram, Javed Riazuddin, Sheikh Ayuso, Carmen Pierce, Eric A. Hardcastle, Alison J. Riazuddin, S. Amer Frazer, Kelly A. Hejtmancik, J. Fielding Rivolta, Carlo Bujakowska, Kinga M. Arno, Gavin Webster, Andrew R. Ayyagari, Radha |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Malka, Samantha Biswas, Pooja Berry, Anne Marie Sangermano, Riccardo Ullah, Mukhtar Lin, Siying D'Antonio, Matteo Jestin, Aleksandr Jiao, Xiaodong Quinodoz, Mathieu Sullivan, Lori Gardner, Jessica C. Place, Emily M. Michaelides, Michel Kaminska, Karolina Mahroo, Omar A. Schiff, Elena Wright, Genevieve Cancellieri, Francesca Vaclavik, Veronika Santos, Cristina Rehman, Atta Ur Mehrotra, Sudeep Azhar Baig, Hafiz Muhammad Iqbal, Muhammad Ansar, Muhammad Santos, Luisa Coutinho Sousa, Ana Berta Tran, Viet H. Matsui, Hiroko Bhatia, Anjana Naeem, Muhammad Asif Akram, Shehla J. Akram, Javed Riazuddin, Sheikh Ayuso, Carmen Pierce, Eric A. Hardcastle, Alison J. Riazuddin, S. Amer Frazer, Kelly A. Hejtmancik, J. Fielding Rivolta, Carlo Bujakowska, Kinga M. Arno, Gavin Webster, Andrew R. Ayyagari, Radha |
| dc.subject.por.fl_str_mv |
African ancestry ancestral allele ciliopathy equity of genetic testing ethnic genetic diversity gene expression non-coding genetic variation retinal dystrophy retinitis pigmentosa South Asian Genetics Genetics(clinical) |
| topic |
African ancestry ancestral allele ciliopathy equity of genetic testing ethnic genetic diversity gene expression non-coding genetic variation retinal dystrophy retinitis pigmentosa South Asian Genetics Genetics(clinical) |
| description |
Publisher Copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. |
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2024 |
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2024-09-30T22:28:48Z 2024-09-05 2024-09-05T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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http://hdl.handle.net/10362/172704 |
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eng |
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eng |
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1537-6605 PURE: 99518474 https://doi.org/10.1016/j.ajhg.2024.07.020 |
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