Background: The majority of studies on the retina-specific ATP-binding casse tte transporter (ABCA4) gene have focussed on molecular genetic analysis; compar atively few studies have described the clinical aspects of ...Background: The majority of studies on the retina-specific ATP-binding casse tte transporter (ABCA4) gene have focussed on molecular genetic analysis; compar atively few studies have described the clinical aspects of ABCA4-associated ret inal disorders. In this study, we demonstrate the spectrum of retinal dystrophie s associated with ABCA4 gene mutations. Methods: Nine well-documented patients representing distinct phenotypes in the continuum of ABCA4-related disorders we re selected. All patients received an extensive ophthalmologic evaluation, inclu ding kinetic perimetry, fluorescein angiography, and electroretinography (ERG). Mutation analysis had been performed previously with the genotyping microarray ( ABCR400 chip) and/or single-strand conformation polymorphism analysis in combin ation with direct DNA sequencing. Results: In all patients, at least one patholo gic ABCA4 mutation was identified. Patient 10034 represented the mild end of the phenotypic spectrum, demonstrating exudative age-related macular degeneration (AMD). Patient 24481 received the diagnosis of late-onset fundus flavimaculatus (FFM), patient 15168 demonstrated the typical FFM phenotype, and patient 19504 had autosomal recessive Stargardt disease (STGD1). Patients 11302 and 7608 exhib ited progression from FFM/STGD1 to cone-rod dystrophy (CRD). A more typical CRD phenotype was found in patients 15680 and 12608. Finally, the most severe ABCA4 -associated phenotype was retinitis pigmentosa (RP) in patient 11366. This phen otype was characterised by extensive atrophy with almost complete loss of periph eral and central retinal functions. Conclusion: We describe nine patients during different stages of disease progression; together, these patients form a contin uum of ABCA4-associated phenotypes. Besides characteristic disorders such as FF M/STGD1, CRD and RP, intermediate phenotypes may be encountered. Moreover, as th e disease progresses, marked differences may be observed between initially compa rable phenotypes. In contrast, distinctly different phenotypes may converge to a similar final stage, characterised by extensive chorioretinal atrophy and very low visual functions. The identified ABCA4 mutations in most, but not all, patie nts were compatible with the resulting phenotypes, as predicted by the genotype -phenotype model for ABCA4-associated disorders. With the advent of therapeuti c options, recognition by the general ophthalmologist of the various retinal phe notypes associated with ABCA4 mutations is becoming increasingly important.展开更多
文摘Background: The majority of studies on the retina-specific ATP-binding casse tte transporter (ABCA4) gene have focussed on molecular genetic analysis; compar atively few studies have described the clinical aspects of ABCA4-associated ret inal disorders. In this study, we demonstrate the spectrum of retinal dystrophie s associated with ABCA4 gene mutations. Methods: Nine well-documented patients representing distinct phenotypes in the continuum of ABCA4-related disorders we re selected. All patients received an extensive ophthalmologic evaluation, inclu ding kinetic perimetry, fluorescein angiography, and electroretinography (ERG). Mutation analysis had been performed previously with the genotyping microarray ( ABCR400 chip) and/or single-strand conformation polymorphism analysis in combin ation with direct DNA sequencing. Results: In all patients, at least one patholo gic ABCA4 mutation was identified. Patient 10034 represented the mild end of the phenotypic spectrum, demonstrating exudative age-related macular degeneration (AMD). Patient 24481 received the diagnosis of late-onset fundus flavimaculatus (FFM), patient 15168 demonstrated the typical FFM phenotype, and patient 19504 had autosomal recessive Stargardt disease (STGD1). Patients 11302 and 7608 exhib ited progression from FFM/STGD1 to cone-rod dystrophy (CRD). A more typical CRD phenotype was found in patients 15680 and 12608. Finally, the most severe ABCA4 -associated phenotype was retinitis pigmentosa (RP) in patient 11366. This phen otype was characterised by extensive atrophy with almost complete loss of periph eral and central retinal functions. Conclusion: We describe nine patients during different stages of disease progression; together, these patients form a contin uum of ABCA4-associated phenotypes. Besides characteristic disorders such as FF M/STGD1, CRD and RP, intermediate phenotypes may be encountered. Moreover, as th e disease progresses, marked differences may be observed between initially compa rable phenotypes. In contrast, distinctly different phenotypes may converge to a similar final stage, characterised by extensive chorioretinal atrophy and very low visual functions. The identified ABCA4 mutations in most, but not all, patie nts were compatible with the resulting phenotypes, as predicted by the genotype -phenotype model for ABCA4-associated disorders. With the advent of therapeuti c options, recognition by the general ophthalmologist of the various retinal phe notypes associated with ABCA4 mutations is becoming increasingly important.
