Unveiling a TGFBI Variant in the Retinal Capillary Hemangioblastoma, Type II Granular Corneal Dystrophy, and Von Hippel-Lindau Families: Unlocking Potential for Early Intervention and Targeted Therapy.

Purpose: To identify the potential genetic factors responsible for retinal capillary hemangioblastoma (RCH) and Type II granular corneal dystrophy (GCDII), with autosomal dominant inheritance. We used whole-exome sequencing (WES) in an Iranian family to identify the possible genetic etiology of RCH and GCDII with other manifestations of von Hippel-Lindau (VHL) disease.

Methods: This study included one Iranian family for WES in index patients and Sanger sequencing in all available individuals.

Results: Clinical presentations of these patients included RCH, GCD, central nervous system hemangioblastoma as well as pancreatic cyst. WES disclosed a heterozygous known pathogenic variant c.371G>A (p.R124H) in exon 4 of gene TGFBI.

Conclusions: For the first time, our research identified the potential involvement of TGFBI: c.371G>A (p.R124H) in an Iranian family with RCH, GCDII, and other symptoms of VHL disease. In the future, TGFBI could offer a new understanding and a promising therapeutic approach for both GCDII and VHL diseases simultaneously. Before using the variant in genetic counseling, it is recommended to conduct functional analysis using appropriate animal models to understand its pathogenesis mechanism.