Identification of a novel homozygous nonsense mutation in the CDHR1 gene in a Chinese family with autosomal recessive retinitis pigmentosa

Background: Retinitis pigmentosa (RP) is a group of hereditary retinal diseases that often lead to blindness. Although 80 genes associated with RP have been observed, the genetic mechanism of approximately 40% RP cases remains unknown. This study was to investigate the disease-causing gene in a Han Chinese family with autosomal recessive RP (arRP).

Methods: A Chinese arRP family (RP-2373), consisting of three affected siblings and eight unaffected family members, was recruited in this study. All participants underwent complete ophthalmic examinations, including visual field testing, best-corrected visual acuity, fundus photography and electroretinography. Whole exome sequencing was performed on the three patients and Sanger sequencing was utilized to confirm the mutations identified in all family members and 2010 unrelated controls.

Results: A novel homozygous nonsense mutation, c.1231C > T (p.Q411X) in the Cadherin-Related Family Member 1 (CDHR1) gene was identified in the RP-2373 family. The proband and her two affected sisters were found to carry a homozygous mutation that led to a substitution of Glutamine to a stop codon. Other unaffected members and 2010 ethnic-matched controls lacked this mutation. These data showed a complete co-segregation of the CDHR1 mutation with arRP in this family. The p.Q411X mutation was observed to affect highly conserved amino acid residue of CHDR1.

Conclusion: Our study expanded the CDHR1 mutation spectrum of RP in the Chinese population, which might help to better understand RP molecular pathogenesis.