The Clinical Manifestation And Molecular Genetics Research Of A Chinese X-link Recessive Retinitis Pigmentosa Family

Purpose: To investigating the phenotype of a Chinese family with X-linked retinitis pigmentosa（XLRP）and identifying the pathogenic gene mutation with Targeted-capture next generation sequencing（Targeted-capture next generation sequencing,Targeted-capture NGS）.Meanwhile,via analyzing the relationship of genotype and phenotype,it is helpful to understand the molecular genetics mechanism of RP.Methods: The diagnosis was produced based on detailed ophthalmic examination of the proband,which covered optical coherence tomography,Automatic perimeter,fundus fluorescein angiography and electroretinogram,in addition to basic ophthalmic examinations.All subjects in this pedigree underwent a systematic history-taking and basic ophthalmic examination,including visual acuity,slit lamp examination,direct ophthalmoscopy and fundus photograph examination.Peripheral venous blood was collected and Targeted-capture NGS was performed on the proband using multigene RP panel contained 57 variants included RP1,RP2,RPGR,RHO,PRPH2,and CRB1.Suspicious mutations were predicted with Bioinformatics Analysis.All variants were verified in the remaining family members by PCR amplification and Sanger sequencing.Results: The four-generation family,a total of 41 members including 6 male patients,inherited as crisscross inheritance trait.All the affected subjects in this pedigree were diagnosed with retinitis pigmentosa（RP）,The male patients showed symptoms from the first decade while the carrier females onset from the second decade or later,which correspond to Lyons Phenomenon（X chromosome inactivation,XCI）.The frameshifted mutation c.345₃48 delTGAA in the RPGR gene was found in all the affected males and female carriers.Bioinformatics analysis demonstrated the mutation produce truncated proteins with novel and shorten amino acid sequences,which lead to lose of functional group and performed as severe disfunction.Conclusion: The novel mutation c.345₃48 delTGAA of the RPGR gene was identified in the Chinese pedigree.The results expand the mutation spectrum of RPGR gene as well as their associated clinical phenotypes in Chinese patients.X chromosome lyonzation（X chromosome inactivation）is a reasonable explanation to female carriers with delayed onset of disease and various phenotypes from asymptomatic to varying extent of RP abnormality.