ABCMdb

PMID: 21510770

Burke TR, Tsang SH
Allelic and phenotypic heterogeneity in ABCA4 mutations.
Ophthalmic Genet. 2011 Sep;32(3):165-74. doi: 10.3109/13816810.2011.565397. Epub 2011 Apr 21., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro ABCA4 p.Cys1490Tyr ABCA4 p.Arg602Trp ABCA4 p.Asn965Ser The most common, L541P/A1038V, has been reported as a founder mutation in Hungaro-German populations.14,16,17 Furthermore "ethnic group-specific" ABCA4 alleles have been described in other populations also, C1490Y and R602W in South African patients,18 and N965S in a Danish population19 among others.20 In an attempt to explain the variability seen in ABCA4 retinal phenotypes and to correlate this with individual mutation effect, a model was proposed which correlated disease severity with residual ABCA4 function.14,21 Maugeri classified ABCA4 mutant alleles as "mild", "moderate", and "severe" based on the predicted effect of the mutation on the transport function of the protein, ie, the more severe the effect of the mutation on ABCA4 function, the more aggressive the disease phenotype. Login to comment 66 ABCA4 p.Gly1961Glu The G1961E missense mutation, the most commonly detected mutation in the ABCA4 gene,31,33,41 may not be associated with the presence of a dark choroid, as well as having more localized and less severe disease phenotype.42-44 Where extensive disease is present there can be difficulty identifying the presence or absence of a silent choroid on FA in the presence of numerous window defects and staining of the flecks during the course of angiography.45 The presence of a ring of hypofluorescence in the peripapillary region on FA has been reported in 37% of patients in a cohort of patients with STGD.45 It was detected at a higher frequency in patients with more severe disease, and was associated with poorer visual acuity and greater visual field defects. Login to comment