Case Report: novel GUCA1B and ABHD12 mutations in retinitis pigmentosa sine pigmento: expanding the genotypic spectrum through multimodal phenotyping

Retinitis pigmentosa sine pigmento (RPSP) is a atypical variant of inherited retinal degeneration characterized by the absence of retinal pigment deposits observed in typical retinitis pigmentosa, which poses significant challenges to clinical diagnosis and genetic investigation. Although high-throughput sequencing technologies have revolutionized the identification of disease-causing genes, studies on RPSP are limited. Therefore, this study aimed to analyze the clinical manifestations and genetic profiles of two patients with RPSP. Two novel potential disease-causing mutations were identified. Patient 1 had a heterozygous missense mutation (c.45G > C, p.Glu15Asp) in the GUCA1B gene, whereas Patient 2 had a homozygous frameshift insertion mutation (c.134_137dupCGGC, p.Ala47Glyfs*4) in the ABHD12 gene. Multimodal imaging techniques, including optical coherence tomography, fundus autofluorescence, adaptive optics scanning laser ophthalmoscope, and fluorescein angiography, combined with visual electrophysiological assessments revealed the structural and functional retinal alterations associated with RPSP. Bioinformatics analysis revealed that these mutations can respectively contributed to disease development by affecting calcium ion regulation in photoreceptor cells and by influencing the hydrolyzing of lysophosphatidylserine (lyso-PS). This study is the first to link novel mutations in GUCA1B and ABHD12 to RPSP. The findings highlight the critical importance of integrating multimodal imaging with genetic profiling in enhancing early diagnostic accuracy and refining genetic counseling strategies for this understudied condition.