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Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region
Strabismus is a common condition, affecting 1%–4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is ba...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685624/ https://www.ncbi.nlm.nih.gov/pubmed/33257509 http://dx.doi.org/10.1136/jmedgenet-2020-107226 |
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author | Ye, Xin (Cynthia) Roslin, Nicole M Paterson, Andrew D Lyons, Christopher J Pegado, Victor Richmond, Phillip Shyr, Casper Fornes, Oriol Han, XiaoHua Higginson, Michelle Ross, Colin J Giaschi, Deborah Gregory-Evans, Cheryl Patel, Millan S Wasserman, Wyeth W |
author_facet | Ye, Xin (Cynthia) Roslin, Nicole M Paterson, Andrew D Lyons, Christopher J Pegado, Victor Richmond, Phillip Shyr, Casper Fornes, Oriol Han, XiaoHua Higginson, Michelle Ross, Colin J Giaschi, Deborah Gregory-Evans, Cheryl Patel, Millan S Wasserman, Wyeth W |
author_sort | Ye, Xin (Cynthia) |
collection | PubMed |
description | Strabismus is a common condition, affecting 1%–4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is based on a seven-generation family with isolated strabismus inherited in an autosomal dominant manner. A total of 13 individuals from a common ancestor have been included for linkage analysis. Among these, nine are affected and four are unaffected. A single linkage signal has been identified at an 8.5 Mb region of chromosome 14q12 with a multipoint LOD (logarithm of the odds) score of 4.69. Disruption of this locus is known to cause FOXG1 syndrome (or congenital Rett syndrome; OMIM #613454 and *164874), in which 84% of affected individuals present with strabismus. With the incorporation of next-generation sequencing and in-depth bioinformatic analyses, a 4 bp non-coding deletion was prioritised as the top candidate for the observed strabismus phenotype. The deletion is predicted to disrupt regulation of FOXG1, which encodes a transcription factor of the Forkhead family. Suggestive of an autoregulation effect, the disrupted sequence matches the consensus FOXG1 and Forkhead family transcription factor binding site and has been observed in previous ChIP-seq studies to be bound by Foxg1 in early mouse brain development. Future study of this specific deletion may shed light on the regulation of FOXG1 expression and may enhance our understanding of the mechanisms contributing to strabismus and FOXG1 syndrome. |
format | Online Article Text |
id | pubmed-8685624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-86856242022-01-04 Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region Ye, Xin (Cynthia) Roslin, Nicole M Paterson, Andrew D Lyons, Christopher J Pegado, Victor Richmond, Phillip Shyr, Casper Fornes, Oriol Han, XiaoHua Higginson, Michelle Ross, Colin J Giaschi, Deborah Gregory-Evans, Cheryl Patel, Millan S Wasserman, Wyeth W J Med Genet Genome-Wide Studies Strabismus is a common condition, affecting 1%–4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is based on a seven-generation family with isolated strabismus inherited in an autosomal dominant manner. A total of 13 individuals from a common ancestor have been included for linkage analysis. Among these, nine are affected and four are unaffected. A single linkage signal has been identified at an 8.5 Mb region of chromosome 14q12 with a multipoint LOD (logarithm of the odds) score of 4.69. Disruption of this locus is known to cause FOXG1 syndrome (or congenital Rett syndrome; OMIM #613454 and *164874), in which 84% of affected individuals present with strabismus. With the incorporation of next-generation sequencing and in-depth bioinformatic analyses, a 4 bp non-coding deletion was prioritised as the top candidate for the observed strabismus phenotype. The deletion is predicted to disrupt regulation of FOXG1, which encodes a transcription factor of the Forkhead family. Suggestive of an autoregulation effect, the disrupted sequence matches the consensus FOXG1 and Forkhead family transcription factor binding site and has been observed in previous ChIP-seq studies to be bound by Foxg1 in early mouse brain development. Future study of this specific deletion may shed light on the regulation of FOXG1 expression and may enhance our understanding of the mechanisms contributing to strabismus and FOXG1 syndrome. BMJ Publishing Group 2022-01 2020-11-30 /pmc/articles/PMC8685624/ /pubmed/33257509 http://dx.doi.org/10.1136/jmedgenet-2020-107226 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Genome-Wide Studies Ye, Xin (Cynthia) Roslin, Nicole M Paterson, Andrew D Lyons, Christopher J Pegado, Victor Richmond, Phillip Shyr, Casper Fornes, Oriol Han, XiaoHua Higginson, Michelle Ross, Colin J Giaschi, Deborah Gregory-Evans, Cheryl Patel, Millan S Wasserman, Wyeth W Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region |
title | Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region |
title_full | Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region |
title_fullStr | Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region |
title_full_unstemmed | Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region |
title_short | Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region |
title_sort | linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with foxg1 syndrome region |
topic | Genome-Wide Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685624/ https://www.ncbi.nlm.nih.gov/pubmed/33257509 http://dx.doi.org/10.1136/jmedgenet-2020-107226 |
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