Search

Purpose: To describe the clinical and molecular genetic characteristics of a large cohort of Chinese patients with choroideremia (CHM)., Methods: Forty-eight Chinese participants from 35 families with a clinical diagnosis of CHM who harbored sequence variants in the CHM gene were enrolled. Comprehensive clinical evaluations and molecular genetic analysis of the CHM gene were performed., Results: The median age of the 48 patients was 31.5 years (range, 5-78 years). There were 30 different sequence variants detected in 35 families; of which, 13 sequence variants were novel. The mean (±SD) best-corrected visual acuity best in logarithm of the minimum angle of resolution equivalents was 0.71 (±0.87) (range, 0.00-2.80) or approximately 20/100 in Snellen visual acuity. A significant correlation was revealed between best-corrected visual acuity best and age (P < 0.001). The trend in the change in the best-corrected visual acuity over age showed that relatively good vision remained until 20 years old. The patterns of fundus photography and fundus autofluorescence finding demonstrated that residual retinal pigment epithelium areas significantly declined in patients at the age of 20 years or older. The results of visual field and full-field electroretinography showed that these measures might be of limited value for evaluating the condition of the late stage of CHM in Chinese patients., Conclusion: This study described for the first time the clinical and molecular genetic characteristics of a large cohort of Chinese patients with CHM. The findings from best-corrected visual acuity best and visual field showed that the impairment of visual function in CHM might be more severe in Chinese patients than in western patients.

Choroidermia (CHM) is an X-linked chorioretinal disorder caused by mutations in the Rab Escort Protein 1 (Rep-1) gene. Its diagnosis depends on clinical findings and genetic confirmation; however, mutations in Rep-1 gene are not always detected by standard Sanger sequencing. We therefore conducted multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR (QPCR) in cases of Chinese CHM families in which sequencing all the exons and flanking intronic regions of the CHM gene had not identified a mutation or exons could not be amplified. We hypothesized that copy number variation (CNV) within the Rep-1 gene would explain the etiology of choroideremia in these patients. In the eight unrelated families, exon deletions or duplications were detected by MLPA and QPCR in five. Our results showed CNV within the Rep-1 gene could be an important contributor in Chinese CHM patients. Sequencing of the Rep-1 gene supplemented with MLPA is therefore an important diagnostic strategy in choroideremia patients., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose: To describe the phenotype and genotype of three Mainland Chinese families affected by choroideremia (CHM)., Methods: Complete ophthalmic examinations were conducted in three unrelated Chinese families with CHM. Peripheral blood samples were collected from the families for genetic and immunoblot analysis. All exons and flanking intronic regions of the gene encoding Rab escort protein-1 (Rep-1) were amplified with PCR and screened for mutations with Sanger sequencing. The three-dimensional structure of mutated Rep-1 was modeled using sequence homology with rat proteins to analyze the effect of the mutation detected in one family., Results: All affected males had characteristic signs and symptoms of CHM; however, central visual acuity impairment occurred earlier than expected. All female carriers older than 45 years had pigmentary changes, and one female carrier was symptomatic with vision loss. Three different mutations in Rep-1, c.1801-1G>A, c.1130 T>A, and c.612delAG, were detected in the three families., Conclusions: In Mainland Chinese families, the central visual acuity of male patients with CHM can be affected at an early age (second decade), whereas female CHM carriers may manifest signs and symptoms at a later age (≥ 45 years). One previously reported and two novel Rep-1 mutations were detected in three Chinese patients with CHM.

Choroideremia (CHM) is a chorioretinal degeneration with an X-linked pattern of inheritance. Affected males experience progressive atrophy of the choroid, retinal pigment epithelium and retina leading to eventual blindness. The CHM gene encodes Rab escort protein 1 (REP-1). REP-1 is involved in trafficking of Rab proteins in the cell. To date, the majority of reported mutations in the CHM gene cause a complete loss of REP-1 function. Here we report pathogenic mutations: a novel missense mutation, L550P; a truncation c.1542T>A, STOP; and two deletions (c.525&#95;526delAG and c.1646delC) in the CHM gene and their phenotypic effect. To analyze the effect of mutations, the 3D structure of human REP-1 and the proteins associated with REP-1 function were modeled using sequence homology with rat proteins. In silico analysis of the missense mutation L550P suggests that the proline residue at position 550 destabilizes the beta-structural elements, and the REP-1 tertiary structure. Truncation and deletion mutants are associated with a partial or total loss of the REP-1 essential activity and protein-protein interactions as predicted by the analysis of the structure and stability of these protein products. The presumptive loss of protein was confirmed by Western Blot analysis of protein from mononuclear cells and fibroblasts (FB) from CHM patients.