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Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity

X-linked myopia 26 (Myopia 26, MIM #301010), which is caused by the variants of ARR3 (MIM *301770), is characterized by female-limited early-onset high myopia (eo-HM). Clinical characteristics include a tigroid appearance in the fundus and a temporal crescent of the optic nerve head. At present, the...

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Autores principales: Xiao, Xuan, Yang, Jingmin, Li, Ying, Yang, Hongxia, Zhu, Yijian, Li, Lianbing, Zhou, Qinlinglan, Lu, Daru, Chen, Ting, Tian, Yafei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917903/
https://www.ncbi.nlm.nih.gov/pubmed/36769483
http://dx.doi.org/10.3390/jcm12030835
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author Xiao, Xuan
Yang, Jingmin
Li, Ying
Yang, Hongxia
Zhu, Yijian
Li, Lianbing
Zhou, Qinlinglan
Lu, Daru
Chen, Ting
Tian, Yafei
author_facet Xiao, Xuan
Yang, Jingmin
Li, Ying
Yang, Hongxia
Zhu, Yijian
Li, Lianbing
Zhou, Qinlinglan
Lu, Daru
Chen, Ting
Tian, Yafei
author_sort Xiao, Xuan
collection PubMed
description X-linked myopia 26 (Myopia 26, MIM #301010), which is caused by the variants of ARR3 (MIM *301770), is characterized by female-limited early-onset high myopia (eo-HM). Clinical characteristics include a tigroid appearance in the fundus and a temporal crescent of the optic nerve head. At present, the limited literature on eo-HM caused by ARR3 mutations shows that its inheritance mode is complex, which brings certain difficulties to pre-pregnancy genetic counseling, pre-implantation genetic diagnosis, and prenatal diagnosis. Here, we investigated the genetic underpinning of a Chinese family with eo-HM. Whole exome sequencing of the proband revealed a novel frameshift mutation in ARR3 (NM_004312, exon10, c.666delC, p. Asn222LysfsTer22). Although the mode of inheritance of the eo-HM family fits the X-linked pattern of ARR3, the phenotypes of three patients deviate from the typical early-onset high myopia. Through X-chromosome inactivation experiments, the patient’s different phenotypes can be precisely explained. In addition, this study not only enhanced the correlation between ARR3 and early-onset high myopia but also provided explanations for different phenotypes, which may inspire follow-up studies. Our results enrich the knowledge of the variant spectrum in ARR3 and provide critical information for preimplantation and prenatal genetic testing, diagnosis, and counseling.
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spelling pubmed-99179032023-02-11 Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity Xiao, Xuan Yang, Jingmin Li, Ying Yang, Hongxia Zhu, Yijian Li, Lianbing Zhou, Qinlinglan Lu, Daru Chen, Ting Tian, Yafei J Clin Med Article X-linked myopia 26 (Myopia 26, MIM #301010), which is caused by the variants of ARR3 (MIM *301770), is characterized by female-limited early-onset high myopia (eo-HM). Clinical characteristics include a tigroid appearance in the fundus and a temporal crescent of the optic nerve head. At present, the limited literature on eo-HM caused by ARR3 mutations shows that its inheritance mode is complex, which brings certain difficulties to pre-pregnancy genetic counseling, pre-implantation genetic diagnosis, and prenatal diagnosis. Here, we investigated the genetic underpinning of a Chinese family with eo-HM. Whole exome sequencing of the proband revealed a novel frameshift mutation in ARR3 (NM_004312, exon10, c.666delC, p. Asn222LysfsTer22). Although the mode of inheritance of the eo-HM family fits the X-linked pattern of ARR3, the phenotypes of three patients deviate from the typical early-onset high myopia. Through X-chromosome inactivation experiments, the patient’s different phenotypes can be precisely explained. In addition, this study not only enhanced the correlation between ARR3 and early-onset high myopia but also provided explanations for different phenotypes, which may inspire follow-up studies. Our results enrich the knowledge of the variant spectrum in ARR3 and provide critical information for preimplantation and prenatal genetic testing, diagnosis, and counseling. MDPI 2023-01-20 /pmc/articles/PMC9917903/ /pubmed/36769483 http://dx.doi.org/10.3390/jcm12030835 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xiao, Xuan
Yang, Jingmin
Li, Ying
Yang, Hongxia
Zhu, Yijian
Li, Lianbing
Zhou, Qinlinglan
Lu, Daru
Chen, Ting
Tian, Yafei
Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity
title Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity
title_full Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity
title_fullStr Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity
title_full_unstemmed Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity
title_short Identification of a Novel Frameshift Variant of ARR3 Related to X-Linked Female-Limited Early-Onset High Myopia and Study on the Effect of X Chromosome Inactivation on the Myopia Severity
title_sort identification of a novel frameshift variant of arr3 related to x-linked female-limited early-onset high myopia and study on the effect of x chromosome inactivation on the myopia severity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917903/
https://www.ncbi.nlm.nih.gov/pubmed/36769483
http://dx.doi.org/10.3390/jcm12030835
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