Phenotypic variation in a family with homogeneous ABCA4 mutations

Poster Details

First Author: M.Lopez Molina SPAIN

Co Author(s):    R. Riveiro Alvarez                             

Abstract Details


To explore the clinical courses and to correlate with the genotype of the three siblings, in order to describe clinical variability of their inherited retinal dystrophy.


17th Euretina Congress Barcelona


Phenotypic variables recorded were age at onset, best-corrected visual acuity (BCVA), fundus autofluorescence (FAF) appearance, electrophysiology, visual fields and optical coherence tomography (OCT). Molecular characterization was performed using a combination of ABCR400 genotyping microarray, high resolution melting screening (HRM) and further analysis by next generation sequencing (NGS).


The three individuals were compound heterozygous for missense variants in the ABCA4 gene: c.3386G>T p.Arg1129Leu and c.5318C>T p.Ala1773Val. The first sibling with clinically diagnosed cone-rod dystrophy (CRD) has the worst BCVA, onset at 12 years of age, with cone and rod moderate and mild diminished amplitudes, central scotomas, an extended area of macular atrophy and flecks outside the vascular arcades. The second sibling has a typical Stargardt disease (STGD) fundus appearance with a smaller area of macular atrophy and perimacular flecks, first symptoms at 27 years and normal electroretinogram. The third sibling has non-recordable rods and a very mild cone response, age of onset 24 years, annular scotoma, vascular attenuation and bone spicule pigmentation, being diagnosed as retinitis pigmentosa (RP).


Mutations in ABCA4 are mainly associated to autosomal recessive STGD and CRD, and to RP in more evolved cases. However, in this family we would expect a more similar phenotype of the three individuals as they carry the same mutations. In consequence, we can not rule out the existence of additional genetic factors modulating their phenotype. Moreover, the existence of other mutations in different genes not analysed for this family cannot be excluded, as the mutational load for retinal diseases is known to be considerable.

Back to previous
EURETINA, Temple House, Temple Road, Blackrock, Co Dublin. | Phone: 00353 1 2100092 | Fax: 00353 1 2091112 | Email:

Privacy policyHotel Terms and Conditions Cancellation policy