Mutation Spectrum of the CHM Gene in Patients With Choroideremia

Abstract

Purpose:: To identify the mutation spectrum of the CHM gene in patients with choroideremia

Methods:: Sixty-six patients with choroideremia belonging to 53 unrelated families were screened for mutations in CHM. Genomic DNA was extracted from leukocytes and mutational screening was performed after amplification of all 15 exons of the CHM gene by PCR using primers located in introns. Exons and splice site boundaries were sequenced.

Results:: Forty mutations of which 24 were novel were identified in the CHM gene in 49 of the 53 unrelated families. All the identified mutations are null. In addition, a missense change (Leu457Pro) was identified in one of the four unsolved families, the significance of which remains to be determined. The most common type of mutation is a small insertion or deletion which occurred in 35% of cases (17/49) followed by nonsense mutations in 33% (16/49). A deletion of one or more exons occurred in 20% (10/49); deletion of the entire CHM gene was identified in two of these families. Splice mutations were present in 12% (6/49). Deleterious changes were located throughout the CHM gene. Exon 6, the most frequently implicated exon, was altered in 16 families (33%).

Conclusions:: We have identified deleterious null mutations in over 90 % of the 53 families clinically diagnosed with choroideremia. Results of clinical assessment of these patients are under analysis in order to see if we can detect any genotype-phenotype correlations.

Keywords: retina • mutations