Purchase this article with an account.
Kaoru Fujinami, Panagiotis I. Sergouniotis, Donna S. Mackay, Alice E. Davidson, Anthony T. Moore, Anthony G. Robson, Graham E. Holder, Michel Michaelides, Andrew R. Webster; The Clinical Effect of Homozygous ABCA4 Alleles in 14 Patients. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4567.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To report the phenotypic findings in a group of patients with homozygous ABCA4 alleles. Retinopathy due to mutation of ABCA4 is highly variable. The common occurrence of heterozygous variants hinders the determination of the severity of specific mutations. Thus a cohort of individuals with homozygous variants was ascertained to gain insight into the retinopathy caused by specific alleles.
A detailed history was obtained. Colour, autofluorescence and SD-OCT imaging was investigated. ISCEV standard electrophysiology was undertaken for functional assessment. An ophthalmoscopic phenotype was assigned based on that reported by Fishman et al. Arch Ophthalmol. 1999. An electrophysiological phenotype was assigned based on the three groups reported by Lois et al. Arch Ophthalmol. 2001. ABCA4 mutation detection was performed with ABCR400 microarray (Asper biotech) and direct sequencing in relatives to assess segregation.
Overall 14/248 individuals (9/202 families) were identified to harbor presumed disease-associated homozygous ABCA4 variants including; p.R1300X, p.Q2220X, IVS28+4 C>T, p.V931M / p.R1705Q, p.R212C, p.C1488R, p.R1640W, p.G1961E. The summarized results of the clinical features are shown in the table. Five out of six patients, homozygous for presumed null alleles had early onset (<10yrs) disease and all six had group 3 electrophysiological phenotypes. Two siblings with p.G1961E had adult-onset disease, the type 1 ophthalmoscopic phenotype and group 1 electrophysiological phenotype.
The phenotypes represented in patients with homozygous variants give insights into individual alleles. Null alleles have severe functional effects, certain missense alleles are similar to nulls, and the common allele, p.G1961E, has a mild structural and functional effect on the adult retina.
This PDF is available to Subscribers Only