Novel INPP5E compound heterozygous mutations cause severe early-onset isolated retinal degeneration: a case report

Abstract Background Pathogenic variants in the INPP5E gene are associated with a broad phenotypic spectrum, from syndromic ciliopathies like Joubert syndrome to non-syndromic inherited retinal degenerations (IRD). Isolated retinal phenotype without systemic involvement remains rarely characterized. We describe a genetically confirmed case of INPP5E related non-syndromic inherited retinal degeneration, with the aim of highlighting that INPP5E variants can present exclusively with retinal degeneration and to delineate its distinct clinical and genetic features, thereby expanding the phenotypic spectrum and providing evidence for genetic counseling. Case presentation A 5-year-old female presented with poor vision and nyctalopia. Ocular examination revealed nystagmus, and peripheral retinal pigmentary disturbances. Imaging showed macular hypoautofluorescence and structural loss of the outer retina on optical coherence tomography. Full-field electroretinography demonstrated nearly extinguished rod and cone responses. Whole-exome sequencing identified novel compound heterozygous mutations in INPP5E : a paternal frameshift variant c.1251del p.Phe418SerfsTer65 and a maternal missense variant c.1861 C > T p.Arg621Trp, both classified as likely pathogenic. Systemic workup was normal, supporting a non-syndromic diagnosis. Conclusions This report describes a severe, early-onset, non-syndromic retinal degeneration associated with novel compound heterozygous INPP5E mutations. The finding expands the mutational and phenotypic spectrum of INPP5E -related disorders and emphasizes the gene’s role in isolated severe retinal dystrophy, highlighting the importance of genetic testing in similar cases.