title: Exome sequencing reveals CHM mutations in six families with atypical choroideremia initially diagnosed as retinitis pigmentosa.
abstract: Mutations in almost 200 genes are associated with hereditary retinal diseases. Of these diseases, retinitis pigmentosa (RP) is the most common and is genetically and clinically highly heterogeneous. At least 62 genes are associated with RP and mutations in these genes account for approximately half of the cases of disease. In the present study, mutations in the CHM gene, which are known to associate with choroideremia, were identified in six of 157 families with retinitis pigmentosa by whole exome sequencing. No potential pathogenic mutations in the 62 RP‑associated genes were found in the six families. Sanger sequencing confirmed the mutations in CHM, including four novel (c.558_559delTT, c.964G>T, c.966delA, c.1166+2T>G) and two known (c.703‑1G>A and c.1584_1587delTGTT) mutations. Available clinical data suggest an atypical phenotype of choroideremia in these patients compared to that of Caucasians. Overlapping clinical features and atypical phenotypic variation may contribute to the confusion of one another. Awareness of the phenotypic variation and careful clinical examination may facilitate proper clinical diagnosis and genetic counseling of complicated hereditary retinal diseases. Whole exome sequencing therefore is useful in the identification of genetic cause for less clarified hereditary retinal diseases and enriches our understanding of phenotypic variations of gene mutation.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Fang
authors.affiliation: BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Panfeng
authors.initials: P
authors.lastname: Wang
authors.affiliation: BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.affiliation: BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D015794:Choroideremia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D059472:Exome / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human