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.
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.
Authors: Jana Zernant; Yajing Angela Xie; Carmen Ayuso; Rosa Riveiro-Alvarez; Miguel-Angel Lopez-Martinez; Francesca Simonelli; Francesco Testa; Michael B Gorin; Samuel P Strom; Mette Bertelsen; Thomas Rosenberg; Philip M Boone; Bo Yuan; Radha Ayyagari; Peter L Nagy; Stephen H Tsang; Peter Gouras; Frederick T Collison; James R Lupski; Gerald A Fishman; Rando Allikmets Journal: Hum Mol Genet Date: 2014-07-31 Impact factor: 6.150
Authors: Di Huang; Jennifer A Thompson; Jason Charng; Enid Chelva; Samuel McLenachan; Shang-Chih Chen; Dan Zhang; Terri L McLaren; Tina M Lamey; Ian J Constable; John N De Roach; May Thandar Aung-Htut; Abbie Adams; Sue Fletcher; Steve D Wilton; Fred K Chen Journal: Mol Genet Genomic Med Date: 2020-04-23 Impact factor: 2.183
Authors: Winston Lee; Yajing Xie; Jana Zernant; Bo Yuan; Srilaxmi Bearelly; Stephen H Tsang; James R Lupski; Rando Allikmets Journal: Hum Genet Date: 2015-11-02 Impact factor: 5.881