Expanding the genetic spectrum of choroideremia in an Australian cohort: report of five novel variants.

Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in the gene. Several 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 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 variant was detected in all families. Eight variants were previously reported, and five were novel. Two variants were identified. We previously reported the molecular confirmation of choroideremia in 11 Australian families. This study expands the genetically confirmed Australian cohort to 32 males and four affected carrier females.