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

• Published in: Human genome variation Vol. 7; no. 1; p. 35
• Main Authors: McLaren, Terri L., De Roach, John N., Thompson, Jennifer A., Chen, Fred K., Mackey, David A., Hoffmann, Ling, Urwin, Isabella R., Lamey, Tina M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.10.2020; Springer Nature B.V
• Subjects: 631/208/1516; 631/208/727; Asymptomatic; Biomedical and Life Sciences; Biomedicine; Clinical trials; Deoxyribonucleic acid; Disease; DNA; Females; Gene banks; Gene Expression; Gene Function; Gene Therapy; Genetics; Genomes; Genotype & phenotype; Human Genetics; Males; Molecular Medicine; Mutation; Genotype; Medical genetics
• ISSN: 2054-345X; 2054-345X
• DOI: 10.1038/s41439-020-00122-w

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. Eye disease: Finding new gene variants for choroideremia Additional variants of the gene responsible for choroideremia, a rare genetic disease that affects blood flow in the eye, have been identified. Choroideremia is X-linked, which means it is much more likely to manifest in males, who do not have a second X chromosome that could carry a functional gene copy. Over time, choroideremia can cause blindness. Terri McLaren at Sir Charles Gairdner Hospital in Perth, Australia, and co-workers aimed to identify new genetic variants that cause choroideremia. Using gene sequencing technology, they identified affected individuals in 14 Australian families, including five new and eight known variants. Prior to sequencing, other eye diseases (excluding choroideremia) had been diagnosed in over one-third of the families, indicating that choroideremia is underdiagnosed. These results will help to build a database of patients for future genetic and other therapies.