A frameshift mutation in the CHM gene causes choroideremia with acute angle‑closure glaucoma

Choroideremia is an X‑linked recessive chorioretinal degenerative disease that is characterized by progressive centripetal loss of the photoreceptor, retinal pigment epithelium (RPE), and choriocapillaris layers. The CHM gene [choroideremia (Rab escort protein 1)] has been identified as the pathogenic gene in choroideremia. The aim of the present study was to describe the clinical and genetic characteristics of a family with choroideremia family. In the present study, a family with choroideremia presenting with serious chorioretinal atrophy and pigment proliferation, shallow anterior chambers, angle closure and high intraocular pressure (IOP) were recruited. The affected family members underwent a complete ophthalmologic examination. DNA samples obtained from the proband II:1 and the patient II:2 were used for targeted exome sequencing of the CHM gene. PCR amplification and Sanger sequencing were used to validate the variations exhibited in family members and controls. A novel frameshift mutation c.280delA (p.Thr94LeufsTer32), in CHM was identified in the male proband, the normal carrier I:2 and the phenotyped carrier II:2, which was absent in the normal individual II:3 as well as in 200 normal controls. Comparing the amino acid sequences of CHM between multiple species through Clustal Omega indicated conserved amino acids in these mutant sites. Additionally, an X‑chromosome inactivation (XCI) assay was performed in the female carriers in the family, in which DNA of the abnormal carrier II:2 and normal carrier I:2 showed a random XCI pattern. To conclude, the present findings strongly indicate that the c.280delA mutation is a disease‑causing mutation in our choroideremia pedigree with acute angle‑closure glaucoma.