Genetic analysis of choroideremia families
Reviewed by Anjali Gupta

Choroideremia (CHM) is a rare X linked recessive chorioretinal dystrophy. Symptoms include nyctalopia and progressive peripheral field loss. Female carriers may have mild symptoms. Choroideremia is known to be caused by a mutation in the CHM gene. A multicentre human gene replacement clinical trial using an adeno-associated viral vector to deliver the REP1 gene to the retina is in progress with initial results showing improved visual outcomes. With the advent of gene replacement therapy, the need for genetic confirmation of choroideremia and the identification of the specific variant involved is of paramount importance. The aim of this study was to genetically analyse the cohort of families in the Australian Inherited Retinal Disease Register (AIRDR) with a familial diagnosis of choroideremia to determine the disease causing variants. Thirty-two participants from 11 unrelated families (15 affected, 10 carriers, seven unaffected) each with at least one affected male family member with choroideremia were identified and included in the study. Genetic analysis of the CHM gene was performed. Results revealed a CHM gene mutation in all 11 families with each family having a different mutation. Of the 11 mutations, there were four nonsense, four frameshift and three splice site mutations. Five mutations were novel and six had been previously reported. The authors conclude that this work is likely to facilitate access for AIRDR participants and their progeny to CHM gene therapy trials.

Genetic analysis of choroideremia families in the Australian population.
McLaren TL, De Roach JN, Montgomery H, et al.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
2015;43:727-34.