Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations
Standard
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.
in: LIFE SCI ALLIANCE, Jahrgang 6, Nr. 10, e202201814, 10.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations
AU - Usman, Muhammad
AU - Jüschke, Christoph
AU - Song, Fei
AU - Kastrati, Dennis
AU - Owczarek-Lipska, Marta
AU - Eilers, Jannis
AU - Pauleikhoff, Laurenz
AU - Lange, Clemens
AU - Neidhardt, John
N1 - © 2023 Usman et al.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - Male
KW - Female
KW - Humans
KW - X Chromosome Inactivation/genetics
KW - Mutation/genetics
KW - Retinitis Pigmentosa/genetics
KW - Heterozygote
KW - Retinal Cone Photoreceptor Cells
KW - Eye Proteins/genetics
U2 - 10.26508/lsa.202201814
DO - 10.26508/lsa.202201814
M3 - SCORING: Journal article
C2 - 37541846
VL - 6
JO - LIFE SCI ALLIANCE
JF - LIFE SCI ALLIANCE
SN - 2575-1077
IS - 10
M1 - e202201814
ER -
