Phenotypic Divergence in C19ORF44-Associated Retinal Degeneration despite an Identical Genotype: A Case Report.

Abstract

Introduction: C19ORF44 has recently been identified as a gene associated with autosomal recessive inherited retinal disease (IRD). The function of the gene remains poorly understood, and a previously reported case with identical primary genotype demonstrated a Stargardt-like macular dystrophy phenotype.

Case presentation: We describe a 65-year-old Chinese female with long-standing nyctalopia and progressive visual field loss. Multimodal retinal imaging demonstrated a peripheral-predominant retinitis pigmentosa phenotype with relative macular sparing, distinct from the previously reported Stargardt-like macular dystrophy associated with the same genotype. Genetic testing identified compound heterozygous stop-gain and frameshift deletion variants in C19ORF44, both predicted to result in loss of function.

Conclusion: This case demonstrates that identical genotypes (biallelic loss-of-function variants in C19ORF44) can result in markedly different retinal phenotypes, highlighting substantial genotype-phenotype variability in this newly described IRD.