Cargando…
Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations
Progressive degeneration of rod and cone photoreceptors frequently is caused by mutations in the X-chromosomal gene Retinitis Pigmentosa GTPase Regulator (RPGR). Males hemizygous for a RPGR mutation often are affected by Retinitis Pigmentosa (RP), whereas female mutation carriers only occasionally p...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403639/ https://www.ncbi.nlm.nih.gov/pubmed/37541846 http://dx.doi.org/10.26508/lsa.202201814 |
_version_ | 1785085114033635328 |
---|---|
author | Usman, Muhammad Jüschke, Christoph Song, Fei Kastrati, Dennis Owczarek-Lipska, Marta Eilers, Jannis Pauleikhoff, Laurenz Lange, Clemens Neidhardt, John |
author_facet | Usman, Muhammad Jüschke, Christoph Song, Fei Kastrati, Dennis Owczarek-Lipska, Marta Eilers, Jannis Pauleikhoff, Laurenz Lange, Clemens Neidhardt, John |
author_sort | Usman, Muhammad |
collection | PubMed |
description | Progressive degeneration of rod and cone photoreceptors frequently is caused by mutations in the X-chromosomal gene Retinitis Pigmentosa GTPase Regulator (RPGR). Males hemizygous for a RPGR mutation often are affected by Retinitis Pigmentosa (RP), whereas female mutation carriers only occasionally present with severe RP phenotypes. The underlying pathomechanism leading to RP in female carriers is not well understood. Here, we analyzed a three-generation family in which two of three female carriers of a nonsense RPGR mutation presented with RP. Among two cell lines derived from the same female family members, differences were detected in RPGR transcript expression, in localization of RPGR along cilia, as well as in primary cilium length. Significantly, these differences correlated with alterations in X-chromosomal inactivation patterns found in the patient-derived cell lines from females. In summary, our data suggest that skewed X-chromosomal inactivation is an important factor that determines the disease manifestation of RP among female carriers of pathogenic sequence alterations in the RPGR gene. |
format | Online Article Text |
id | pubmed-10403639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-104036392023-08-06 Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations Usman, Muhammad Jüschke, Christoph Song, Fei Kastrati, Dennis Owczarek-Lipska, Marta Eilers, Jannis Pauleikhoff, Laurenz Lange, Clemens Neidhardt, John Life Sci Alliance Research Articles Progressive degeneration of rod and cone photoreceptors frequently is caused by mutations in the X-chromosomal gene Retinitis Pigmentosa GTPase Regulator (RPGR). Males hemizygous for a RPGR mutation often are affected by Retinitis Pigmentosa (RP), whereas female mutation carriers only occasionally present with severe RP phenotypes. The underlying pathomechanism leading to RP in female carriers is not well understood. Here, we analyzed a three-generation family in which two of three female carriers of a nonsense RPGR mutation presented with RP. Among two cell lines derived from the same female family members, differences were detected in RPGR transcript expression, in localization of RPGR along cilia, as well as in primary cilium length. Significantly, these differences correlated with alterations in X-chromosomal inactivation patterns found in the patient-derived cell lines from females. In summary, our data suggest that skewed X-chromosomal inactivation is an important factor that determines the disease manifestation of RP among female carriers of pathogenic sequence alterations in the RPGR gene. Life Science Alliance LLC 2023-08-04 /pmc/articles/PMC10403639/ /pubmed/37541846 http://dx.doi.org/10.26508/lsa.202201814 Text en © 2023 Usman et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Usman, Muhammad Jüschke, Christoph Song, Fei Kastrati, Dennis Owczarek-Lipska, Marta Eilers, Jannis Pauleikhoff, Laurenz Lange, Clemens Neidhardt, John Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations |
title | Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations |
title_full | Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations |
title_fullStr | Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations |
title_full_unstemmed | Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations |
title_short | Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations |
title_sort | skewed x-inactivation is associated with retinal dystrophy in female carriers of rpgr mutations |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403639/ https://www.ncbi.nlm.nih.gov/pubmed/37541846 http://dx.doi.org/10.26508/lsa.202201814 |
work_keys_str_mv | AT usmanmuhammad skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT juschkechristoph skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT songfei skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT kastratidennis skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT owczareklipskamarta skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT eilersjannis skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT pauleikhofflaurenz skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT langeclemens skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations AT neidhardtjohn skewedxinactivationisassociatedwithretinaldystrophyinfemalecarriersofrpgrmutations |