Copy number variant analysis in CHM to detect duplications underlying choroideremia

To investigate the possibility of duplications or deletions within the CHM gene as a cause of choroideremia (CHM).

Eight males and one female subject were identified in whom clinical features were consistent with a clinical diagnosis of CHM. In all cases, sequencing of the coding region and adjacent intronic splice sites did not identify a mutation. In some cases, supplemental immunoblot analysis of protein from peripheral blood leukocytes with anti-REP-1 antibody confirmed absence of Rab escort protein-1, REP-1. A multiplex ligation-dependent probe amplification assay (MLPA) for the CHM gene was developed to test for deletions and duplications within the CHM gene.

A duplication of exons 3-8 of the CHM gene (NM_000390.2) was identified in one case.

While likely an uncommon event, duplication within the CHM gene could be considered as an explanation for CHM cases in which no mutation is found by sequence analysis.