De novo deletion removes a conserved motif in the C-terminus of ABCA4 and results in cone-rod dystrophy.
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 flavimaculatus, 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.
Stenirri
Stefania
S
Unit of Genomics for Diagnosis of Human Pathologies, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Battistella
Stefania
S
Fermo
Isabella
I
Manitto
Maria Pia
MP
Martina
Elisabetta
E
Brancato
Rosario
R
Ferrari
Maurizio
M
Cremonesi
Laura
L