Abstract
Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in the CHM gene. Several CHM gene replacement clinical trials are in advanced stages. In this study, we report the molecular confirmation of choroideremia in 14 Australian families sourced from the Australian Inherited Retinal Disease Registry and DNA Bank. Sixteen males (14 symptomatic) and 18 females (4 symptomatic; 14 obligate carriers) were identified for analysis. Participants’ DNA was analyzed for disease-causing CHM variants by Sanger sequencing, TaqMan qPCR and targeted NGS. We report phenotypic and genotypic data for the 14 symptomatic males and four females manifesting disease symptoms. A pathogenic or likely pathogenic CHM variant was detected in all families. Eight variants were previously reported, and five were novel. Two de novo variants were identified. We previously reported the molecular confirmation of choroideremia in 11 Australian families. This study expands the CHM genetically confirmed Australian cohort to 32 males and four affected carrier females.
Highlights
Choroideremia (CHM, OMIM: 303100) is a chorioretinal dystrophy inherited in an X-linked recessive manner with an incidence between 1:50,0001 and 1:100,0002
Choroideremia is caused by mutations in the CHM gene (OMIM: 300390), which is located at Xq21.2 and comprises 15 exons[5] encoding Rab escort protein 1 (REP-1)
A genetic diagnosis of choroideremia was confirmed for all nine families with a clinical diagnosis of Present study In this study, different CHM variants classified as pathogenic or likely pathogenic were identified in Australian families
Summary
Choroideremia (CHM, OMIM: 303100) is a chorioretinal dystrophy inherited in an X-linked recessive manner with an incidence between 1:50,0001 and 1:100,0002. It is characterized by progressive degeneration of the retinal pigment epithelium (RPE), photoreceptors, and choroid[3]. Choroideremia is caused by mutations in the CHM gene (OMIM: 300390), which is located at Xq21.2 and comprises 15 exons[5] encoding Rab escort protein 1 (REP-1). Due to the monogenic nature and distinctive phenotype of this disease, direct sequencing of the CHM gene, with follow-up deletion/duplication analysis where required, has been highly effective for genetic confirmation of clinically diagnosed individuals[7]. Choroideremia may have a variable phenotype, leading to underreporting[11]
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