A novel compound heterozygous PCDH15 variants may be associated with arRP in a Chinese pedigree

Abstract

Background Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases. However, it is still not well understand about the relationship between PCDH15 mutations and RP. Methods In this study, we enrolled a Chinese autosomal recessive retinitis pigmentosa (arRP) pedigree and identified the causative gene in the proband by targeted whole exome sequencing(WES).The mutations were validated in the family members by Sanger sequencing and co-segregation analysis. Results Novel compound heterozygous, deleterious missense variants of the PCDH15 gene, NM_001384140.1:c.4368 − 2147_4368-2131del and c.2505del(p.T836Lfs*6), were identified in the arRP pedigree, which co-segregated with the clinical RP phenotypes. The PCDH15 protein is highly conserved among species. Conclusion This is the first study to identify novel compound heterozygous mutations c.4368 − 2147_4368-2131del and c.2505del(p.T836Lfs*6) in the PCDH15 gene which might be disease-causing mutations, thereby extending the mutational spectra. All above findings will contribute to genetic counseling, molecular diagnosis and clinical management of arRP disease.