Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations.
Life Sci Alliance
; 6(10)2023 10.
Article
em En
| MEDLINE
| ID: mdl-37541846
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Retinose Pigmentar
/
Inativação do Cromossomo X
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article