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TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations

Precise genetic and phenotypic characterization of congenital stationary night blindness (CSNB) patients is needed for future therapeutic interventions. The aim of this study was to estimate the prevalence of CSNB in our populations and to study clinical and genetic aspects of the autosomal recessiv...

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Autores principales: AlTalbishi, Alaa, Zelinger, Lina, Zeitz, Christina, Hendler, Karen, Namburi, Prasanthi, Audo, Isabelle, Sheffer, Ruth, Yahalom, Claudia, Khateb, Samer, Banin, Eyal, Sharon, Dror
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700182/
https://www.ncbi.nlm.nih.gov/pubmed/31427709
http://dx.doi.org/10.1038/s41598-019-46811-7
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author AlTalbishi, Alaa
Zelinger, Lina
Zeitz, Christina
Hendler, Karen
Namburi, Prasanthi
Audo, Isabelle
Sheffer, Ruth
Yahalom, Claudia
Khateb, Samer
Banin, Eyal
Sharon, Dror
author_facet AlTalbishi, Alaa
Zelinger, Lina
Zeitz, Christina
Hendler, Karen
Namburi, Prasanthi
Audo, Isabelle
Sheffer, Ruth
Yahalom, Claudia
Khateb, Samer
Banin, Eyal
Sharon, Dror
author_sort AlTalbishi, Alaa
collection PubMed
description Precise genetic and phenotypic characterization of congenital stationary night blindness (CSNB) patients is needed for future therapeutic interventions. The aim of this study was to estimate the prevalence of CSNB in our populations and to study clinical and genetic aspects of the autosomal recessive (AR) form of CSNB. This is a retrospective cohort study of Palestinian and Israeli CSNB patients harboring mutations in TRPM1 underwent comprehensive ocular examination. Genetic analysis was performed using homozygosity mapping and sequencing. 161 patients (from 76 families) were recruited for this study, leading to a prevalence of 1:6210 in the vicinity of Jerusalem, much higher than the worldwide prevalence. 61% of the families were consanguineous with AR inheritance pattern. Biallelic pathogenic TRPM1 mutations were identified in 36 families (72 patients). Two founder mutations explain the vast majority of cases: a nonsense mutation c.880A>T (p.Lys294*) identified in 22 Palestinian families and a large genomic deletion (36,445 bp) encompassing exons 2–7 of TRPM1 present in 13 Ashkenazi Jewish families. Most patients were myopic (with mean BCVA of 0.40 LogMAR) and all had absent rod responses in full field electroretinography. To the best of our knowledge, this is the largest report of a clinical and genetic analysis of patients affected with CSNB due to TRPM1 mutations.
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spelling pubmed-67001822019-08-21 TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations AlTalbishi, Alaa Zelinger, Lina Zeitz, Christina Hendler, Karen Namburi, Prasanthi Audo, Isabelle Sheffer, Ruth Yahalom, Claudia Khateb, Samer Banin, Eyal Sharon, Dror Sci Rep Article Precise genetic and phenotypic characterization of congenital stationary night blindness (CSNB) patients is needed for future therapeutic interventions. The aim of this study was to estimate the prevalence of CSNB in our populations and to study clinical and genetic aspects of the autosomal recessive (AR) form of CSNB. This is a retrospective cohort study of Palestinian and Israeli CSNB patients harboring mutations in TRPM1 underwent comprehensive ocular examination. Genetic analysis was performed using homozygosity mapping and sequencing. 161 patients (from 76 families) were recruited for this study, leading to a prevalence of 1:6210 in the vicinity of Jerusalem, much higher than the worldwide prevalence. 61% of the families were consanguineous with AR inheritance pattern. Biallelic pathogenic TRPM1 mutations were identified in 36 families (72 patients). Two founder mutations explain the vast majority of cases: a nonsense mutation c.880A>T (p.Lys294*) identified in 22 Palestinian families and a large genomic deletion (36,445 bp) encompassing exons 2–7 of TRPM1 present in 13 Ashkenazi Jewish families. Most patients were myopic (with mean BCVA of 0.40 LogMAR) and all had absent rod responses in full field electroretinography. To the best of our knowledge, this is the largest report of a clinical and genetic analysis of patients affected with CSNB due to TRPM1 mutations. Nature Publishing Group UK 2019-08-19 /pmc/articles/PMC6700182/ /pubmed/31427709 http://dx.doi.org/10.1038/s41598-019-46811-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
AlTalbishi, Alaa
Zelinger, Lina
Zeitz, Christina
Hendler, Karen
Namburi, Prasanthi
Audo, Isabelle
Sheffer, Ruth
Yahalom, Claudia
Khateb, Samer
Banin, Eyal
Sharon, Dror
TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations
title TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations
title_full TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations
title_fullStr TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations
title_full_unstemmed TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations
title_short TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations
title_sort trpm1 mutations are the most common cause of autosomal recessive congenital stationary night blindness (csnb) in the palestinian and israeli populations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700182/
https://www.ncbi.nlm.nih.gov/pubmed/31427709
http://dx.doi.org/10.1038/s41598-019-46811-7
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