Diagnosis of choroideremia in two Chinese families misdiagnosed as retinitis pigmentosa using next-generation sequencing / 中华实验眼科杂志

ABSTRACT

Objective To identify choroideremia and retinitis pigmentosa ( RP ) using next-generation sequencing( NGS) technology. Methods A cross-sectional study was adopted. The participants were two pedigrees that was suspected of RP in previous hospital treatments in He Eye Specialist Hospital between January 2017 and December 2018. The relevant medical and family history were collected,and the family tree was plotted. The visual acuity, intraocular pressure, fundus photography, electroretinogram ( ERG ) , B-mode ultrasond, visual field, color vision,optical coherence tomography(OCT),and slit lamp assessment were performed on all subjects. Target region sequencing and Sanger sequencing were performed, deletion insertion of large fragments was verified by real-time quantitative PCR. This study followed the Helsinki Declaration and was approved by the Ethics Committee of Shenyang He Eye Hospital(NO. IRB[2017]k002. 01) Results Two known pathogenic mutations were identified in CHM geneEX9 DEL and c. 715C>T. Furthermore, the clinical diagnosis of choroideremia was confirmed. The Family 1 probandⅡ1 with the EX9 DEL hemizygous mutation had a special clinical phenotype,"Star" small piece intact choroid was visible in the macular fovea of both eyes. The patients in pedigree 2 carried the pathogenic mutation c. 715C>T,the probandⅢ1 carried a hemizygous mutation and the reddish island area in the fovea macula was seen in both eyes. The motherⅡ2 and grandmother I2 of proband carried heterozygous mutations,the degree of fundus atrophy was lighter than that of the proband Ⅲ1, the fundus had a mottled appearance, the optic disc boundary was clear, the blood vessel thickness was moderate,and the exposed choroid was visible in the fundus atrophy area. Conclusions This study is the first to identify two known pathogenic mutations in CHM gene,EX9 DEL and c. 715C>T in Asian Manchu and Han populations. The clinical phenotypes of female carriers with the c. 715C>t pathogenic mutation are different from those of male patients. The NGS technology may become a powerful tool to distinguish choroideremia from RP.