Isolated bull's eye maculopathy in two siblings with biallelic TULP1 variants.

INTRODUCTION: TUB-like protein 1 (TULP1) is a protein expressed in rod and cone photoreceptors, where it is thought to play a role in ciliary transport. Pathogenic variants in TULP1 have been implicated in a number of retinal conditions, including non-syndromic retinitis pigmentosa, early-onset retinitis pigmentosa, Leber congenital amaurosis, cone dystrophy, and cone-rod dystrophy. We present two siblings, in whom biallelic likely pathogenic TULP1 variants manifest as an isolated bull's eye maculopathy in the absence of generalized photoreceptor degeneration.

METHODS: Multimodal assessment included ultra-widefield color fundus photography, fundus autofluorescence imaging, spectral domain optical coherence tomography, and full-field electroretinography. Genetic testing was performed with next-generation sequencing retinal gene panel.

RESULTS: We identified a pair of siblings with an isolated bull's eye maculopathy and no functional or anatomic generalized photoreceptor pathology. Genetic testing revealed that each sibling harbored biallelic compound heterozygous likely pathogenic variants in TULP1: c.1376T>C (p.I459T) and c.1471T>C (p.F491L).

CONCLUSIONS: This report expands the phenotypic spectrum of TULP1-associated pathology to include isolated bull's eye maculopathy. To the best of our knowledge, this is the first report of an isolated bull's eye maculopathy associated with a TULP1 molecular diagnosis. Our findings highlight the considerable phenotypic heterogeneity observed in TULP1-related retinal dystrophies.