TY - JOUR
T1 - The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene
AU - Talib, Mays
AU - van Schooneveld, Mary J
AU - Van Cauwenbergh, Caroline
AU - Wijnholds, Jan
AU - Ten Brink, Jacoline B
AU - Florijn, Ralph J
AU - Schalij-Delfos, Nicoline E
AU - Dagnelie, Gislin
AU - van Genderen, Maria M
AU - De Baere, Elfride
AU - Meester-Smoor, Magda A
AU - De Zaeytijd, Julie
AU - Cremers, Frans P M
AU - van den Born, L Ingeborgh
AU - Thiadens, Alberta A
AU - Hoyng, Carel B
AU - Klaver, Caroline C
AU - Leroy, Bart P
AU - Bergen, Arthur A
AU - Boon, Camiel J F
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Purpose: The purpose of this study was to investigate the phenotype and long-term clinical course of female carriers of RPGR mutations.Methods: This was a retrospective cohort study of 125 heterozygous RPGR mutation carriers from 49 families.Results: Eighty-three heterozygotes were from retinitis pigmentosa (RP) pedigrees, 37 were from cone-/cone-rod dystrophy (COD/CORD) pedigrees, and 5 heterozygotes were from pedigrees with mixed RP/CORD or unknown diagnosis. Mutations were located in exon 1-14 and in ORF15 in 42 of 125 (34%) and 83 of 125 (66%) subjects, respectively. The mean age at the first examination was 34.4 years (range, 2.1 to 86.0 years). The median follow-up time in heterozygotes with longitudinal data (n = 62) was 12.2 years (range, 1.1 to 52.2 years). Retinal pigmentary changes were present in 73 (58%) individuals. Visual symptoms were reported in 51 (40%) cases. Subjects with both symptoms and pigmentary fundus changes were older than the other heterozygotes (P = 0.01) and had thinner foveal outer retinas (P = 0.006). Complete expression of the RP or CORD phenotype was observed in 29 (23%) heterozygotes, although usually in milder forms than in affected male relatives. Best-corrected visual acuity (BCVA) was <20/40 and <20/400 in at least one eye in 45 of 116 (39%) and 11 of 116 (9%) heterozygotes, respectively. Myopia was observed in 74 of 101 (73%) subjects and was associated with lower BCVA (P = 0.006). Increasing age was associated with lower BCVA (P = 0.002) and decreasing visual field size (P = 0.012; I4e isopter).Conclusions: RPGR mutations lead to a phenotypic spectrum in female carriers, with myopia as a significantly aggravating factor. Complete disease expression is observed in some individuals, who may benefit from future (gene) therapeutic options.
AB - Purpose: The purpose of this study was to investigate the phenotype and long-term clinical course of female carriers of RPGR mutations.Methods: This was a retrospective cohort study of 125 heterozygous RPGR mutation carriers from 49 families.Results: Eighty-three heterozygotes were from retinitis pigmentosa (RP) pedigrees, 37 were from cone-/cone-rod dystrophy (COD/CORD) pedigrees, and 5 heterozygotes were from pedigrees with mixed RP/CORD or unknown diagnosis. Mutations were located in exon 1-14 and in ORF15 in 42 of 125 (34%) and 83 of 125 (66%) subjects, respectively. The mean age at the first examination was 34.4 years (range, 2.1 to 86.0 years). The median follow-up time in heterozygotes with longitudinal data (n = 62) was 12.2 years (range, 1.1 to 52.2 years). Retinal pigmentary changes were present in 73 (58%) individuals. Visual symptoms were reported in 51 (40%) cases. Subjects with both symptoms and pigmentary fundus changes were older than the other heterozygotes (P = 0.01) and had thinner foveal outer retinas (P = 0.006). Complete expression of the RP or CORD phenotype was observed in 29 (23%) heterozygotes, although usually in milder forms than in affected male relatives. Best-corrected visual acuity (BCVA) was <20/40 and <20/400 in at least one eye in 45 of 116 (39%) and 11 of 116 (9%) heterozygotes, respectively. Myopia was observed in 74 of 101 (73%) subjects and was associated with lower BCVA (P = 0.006). Increasing age was associated with lower BCVA (P = 0.002) and decreasing visual field size (P = 0.012; I4e isopter).Conclusions: RPGR mutations lead to a phenotypic spectrum in female carriers, with myopia as a significantly aggravating factor. Complete disease expression is observed in some individuals, who may benefit from future (gene) therapeutic options.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Child
KW - Child, Preschool
KW - Eye Proteins/genetics
KW - Female
KW - Heterozygote
KW - Humans
KW - Middle Aged
KW - Myopia/complications
KW - Phenotype
KW - Retinal Pigment Epithelium/pathology
KW - Retinitis Pigmentosa/genetics
KW - Retrospective Studies
KW - Visual Acuity/physiology
KW - Young Adult
U2 - 10.1167/iovs.17-23453
DO - 10.1167/iovs.17-23453
M3 - Article
C2 - 30105367
SN - 0146-0404
VL - 59
SP - 4123
EP - 4133
JO - Investigative ophthalmology & visual science
JF - Investigative ophthalmology & visual science
IS - 10
ER -