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Female heterozygotes of X‐linked ocular disease in the era of molecular diagnostics
Author(s) -
KREPS E.O.,
De Zaeytijd J.,
De Baere E.,
Leroy B.P.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0433
Subject(s) - compound heterozygosity , heterozygote advantage , retinitis pigmentosa , fundus (uterus) , medicine , ophthalmology , mutation , retinal , genetics , allele , biology , gene
Purpose To investigate the accuracy of recognizing female heterozygotes for X‐linked retinitis pigmentosa ( XLRP ) and choroideraemia ( CHM ) using fundoscopy and blue‐light fundus autofluorescence ( FAF ). Methods Retrospective analysis revealed 26 female XLRP heterozygotes from 17 different families (age 3–77 years) and 8 CHM heterozygotes from 5 families (age 14–65 years). Molecular diagnosis has been obtained for all subjects. Results In XLRP , 17 of 26 patients (65.4%) mentioned nyctalopia. RPGR mutations were identified in 18 subjects – 9 of which in ORF 15 – whereas a causative mutation was found in RP 2 in the remaining 8 subjects. Dilated fundoscopy showed no abnormalities in 8 subjects, a tapetoid reflex in 2, regional pigmentary changes in 16 and full‐blown RP features in 2 patients. An abnormal FAF pattern was found in 18 of 26 patients (69.2%). Of the 26 molecularly proven heterozygotes, 23 (88.5%) showed abnormalities on fundoscopy and/or FAF . In CHM , only 1 of 8 patients – aged 40 – mentioned visual difficulties at night. In each of the 8 subjects, equatorial mottled pigmentary changes were evident. FAF revealed multiple hyper‐ and hypoautofluorescent flecks in all 8 patients. In both XLRP and CHM , clinical findings were independent of age or specific mutation. Conclusions Female heterozygotes of XLRP show abnormalities on dilated fundoscopy and/or blue‐light fundus autofluorescence in 88.5% of cases with a molecularly proven diagnosis. The most characteristic feature is a radial pattern of alternating areas of hyper‐ and hypoautofluorescence. In CHM , all carriers exhibit pigmentary changes in the retinal midperiphery and scattered autofluorescence changes, despite a lack of visual symptoms.