Next-generation sequencing (NGS) was then applied to two affected family members with RP (III:9 and IV:1), who did not have CYP4V2 mutations, then to identify disease-causing variants in 47 RP-related genes including the PRPF31, CRB1, PRPF8, CA4, TULP1, PRPF3, ABCA4, RPE65, EYS, CERKL, NRL, FAM161A, FSCN2, TOPORS, SNRNP200, SEMA4A, PRCD, NR2E3, MERTK, USH2A, PDE6B, PROM1, KLHL7, PDE6A, RGR, CNGB1, IDH3B, SAG, GUCA1B, CNGA1, BEST1, TTC8, C2orf71, ARL6, IMPG2, PDE6G, ZNF513, DHDDS, PRPF6, CLRN1, MAK, CDHR1, FLVCR1, RLBP1, SPATA7, AIPL1, and LRAT genes.
Two types of clinical and molecular manifestations were observed in this family: (i) a BCD phenotype that was related to the compound heterozygous CYP4V2 mutations and (ii) a RP phenotype that was associated with the PRPF3 mutation and followed an autosomal dominant pattern of inheritance.
Notably, no PRPF3 mutations were detected in the proband.
One PRPF3 mutation, c.1481C>T (p.T494M), was detected in 13 family members, including 11 males and 2 females.
PRPF3 (MIM 607301) is a precursor mRNA-processing factor gene that was first identified for adRP in 2002 .
In the present study, we identified the coexistence of two distinct phenotypes in one family, namely, BCD and RP, which were caused by the pathogenic variants in the CYP4V2 and PRPF3 genes, respectively.
Two types of clinical and molecular manifestations identified in this study include (i) a BCD phenotype related to CYP4V2 mutations and (ii) an RP phenotype related to PRPF3 variants.
Munier, "Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to a T494M mutation in the PRPF3 gene," Molecular Vision, vol.
Hernan et al., "Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa," Investigative Ophthalmology & Visual Science, vol.
Caption: Figure 2: The depth and coverage of next-generation sequencing of the PRPF3 gene and the chromatogram obtained by Sanger sequencing (patient III:9).