Systematic review of genotype-phenotype associations in -associated retinal dystrophies.

BACKGROUND AND OBJECTIVES

-associated retinal dystrophies (-RDs) exhibit significant genotype-phenotype heterogeneity. This study aimed to elucidate the genotype-phenotype associations of through a systematic analysis of the reported cases.

METHODS

84 studies, including 373 worldwide participants, were reviewed. These studies were checked for quality using Murad's tool for methodological quality and synthesis of case series and case reports. Clinical data, fundus imaging characteristics and genetic pathogenic variants were analysed.

RESULTS

The quality analysis revealed an overall good quality of the dataset, with some exceptions that do not detract from this trend. A predominance of cone-rod dystrophy (CRD) and Leber congenital amaurosis (LCA) among -RDs (43% and 27%, respectively) was noted. Missense pathogenic variants were significantly associated with macular pigmentation, an absence of peripheral atrophy, an absence of peripheral pigmentation and CRD (p<0.05). In contrast, the indels (98% frameshifts) were associated with pale optic discs, attenuated optic vessels, and peripheral bone spicules, and more severe phenotypes, such as LCA (p<0.05). Pathogenic variants in the homeodomain were associated with cone and/or CRD; others in the OTX tail were linked to LCA.

CONCLUSION

pathogenic variants are associated with specific phenotypic features.

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