Exome sequencing reveals CHM mutations in six families with atypical choroideremia initially diagnosed as retinitis pigmentosa.

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.