De novo deletion removes a conserved motif in the C-terminus of ABCA4 and results in cone-rod dystrophy

    loading  Checking for direct PDF access through Ovid

Abstract

Background

Mutations in the retina-specific ABC transporter (ABCA4) gene are associated with different types of macular degeneration, including Stargardt disease, cone-rod dystrophy, Fundus flavimacu-latus, Retinitis pigmentosa and probably age-related macular degeneration.

Methods

Screening for mutations in the ABCA4 gene was performed using denaturing high-performance liquid chromatography and direct sequencing.

Results

We describe the identification of a new de novo 44-bp deletion in an Italian patient affected by cone-rod dystrophy. The mutation, located in intron 48 of the ABCA4 gene, is predicted to cause exon 49 skipping, resulting in loss of the C-terminus of the ABCA4 protein. Interestingly, exon 49 also codes for a highly conserved VFVNFA motif, which has been demonstrated to be essential for the activity of ABCA1, another gene of the ABC transporter family. The presence of CT repeats at the breakpoints might have facilitated the generation of the deletion through a slippage mispairing mechanism.

Conclusions

The new 6730-16del44 deletion is the first de novo mutation associated with cone-rod dystrophy and may contribute to a better understanding of the role of ABCA4 mutations in macular dystrophies.

Related Topics

    loading  Loading Related Articles