ABCMdb

PMID: 26377081

Cideciyan AV, Swider M, Schwartz SB, Stone EM, Jacobson SG
Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front.
Invest Ophthalmol Vis Sci. 2015 Sep;56(10):5946-55. doi: 10.1167/iovs.15-17698., [PubMed]

Sentences

No. Mutations Sentence Comment

153 ABCA4 p.Gly1961Glu ABCA4 p.Leu541Pro ABCA4 p.Thr1019Met ABCA4 p.Cys54Tyr ABCA4 p.Arg1640Gln ABCA4 p.Pro1380Leu ABCA4 p.Arg1129Leu ABCA4 p.Pro68Leu example, among the 14 patients compound heterozygous for the common G1961E allele (Supplementary Table S1), the model would predict foveal disease in the first decade of life for three alleles (P68L;G1961E, L541P;A1038V, and T1019M), second decade of life for four alleles (R1129L, C54Y, R152Stop, and V256V) and fourth decade of life for four alleles (P1380L, R1640Q, c.5312&#fe;1 G>A, and M669fs). Login to comment 181 ABCA4 p.Leu541Pro Pigmented Abca4 knockout and L541P;A1038V knockin mice show substantial accumulation of lipofuscin in the RPE but show little, if any, retinal degeneration.61,75 Albino Abca4 knockout mice show both lipofuscin accumulation and a slow photoreceptor degeneration but similarity of photoreceptor loss in homozygote and heterozygote animals do not match the normal retinas of human heterozygote carriers.76-78 Abca4-Rdh8 double-knockout mice show hypersensitivity to acute light damage which has not been observed in human patients.59 Thus, it is currently difficult to extrapolate from preclinical experimental therapies what component and which stages of human disease may successfully be treated with different approaches. Login to comment