ABCMdb

PMID: 25324290

van Huet RA, Bax NM, Westeneng-Van Haaften SC, Muhamad M, Zonneveld-Vrieling MN, Hoefsloot LH, Cremers FP, Boon CJ, Klevering BJ, Hoyng CB
Foveal sparing in Stargardt disease.
Invest Ophthalmol Vis Sci. 2014 Oct 16;55(11):7467-78. doi: 10.1167/iovs.13-13825., [PubMed]

Sentences

No. Mutations Sentence Comment

112 ABCA4 p.Arg2030Gln In contrast, in our cohort we defined foveal sparing as profound RPE atrophy that surrounded the fovea by at least 1808 and spared the fovea`s structure and function. This clinical presentation is a rare finding among STGD1 patients, and our strict selection criterion resulted in a small but homogeneous cohort with a consistent phenotype and excluded STGD1 patients with late-onset disease that began with foveal atrophy. Moreover, our definition of foveal sparing is consistent with previously reported cases of foveal sparing in patients with other degenerative diseases.6,8,33,34 Despite the differences between our cohort and the cohort described by Fujinami et al.,26 the visual acuity and electrophysiology findings in their paper are similar to the findings in our study; nevertheless, none of our patients were carriers of the ABCA4 p.Arg2030Gln missense mutation, which was suggested previously to be prevalent among STGD1 patients with foveal sparing.26 The Etiology of Foveal Sparing In our study, screening the ABCA4 gene identified 19 pathogenic mutations that were described previously in STGD1 and/or other ABCA4-associated retinopathies (Table 2)16,23,35-45 ; interestingly, however, foveal sparing was not described in any of the patients who were previously reported to carry these mutations. Login to comment 114 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Cys1488Arg ABCA4 p.Asn96Asp ABCA4 p.Ile1562Thr ABCA4 p.Val643Gly ABCA4 p.Ile1846Thr ABCA4 p.Arg602Gln ABCA4 p.Phe608Ile ABCA4 p.Phe608Ile ABCA4 p.Cys1455Arg ABCA4 Mutations in STGD1 Patients With Foveal Sparing Allele 1 Allele 2 References DNA Variant Effect DNA Variant Effect P1 c.5461-10TC Unknown NI NA 35, 36 P2 c.3113CT p.Ala1038Val c.3874CT p.Gln1292* 16, 37, 38, 58 P3 c.5461-10TC Unknown c.5537TC p.Ile1846Thr 23, 35, 39, 58 P4 c.4363TC p.Cys1455Arg NI NA 40 P5 c.1822TA p.Phe608Ile c.4685TC p.Ile1562Thr 23, 40, 41, 59 P6 c.768GT Splice defect c.3113CT p.Ala1038Val 16, 23, 37 P7 c.5196&#fe;1GT Splice defect NI NA 45, 58 P8 c.3874CT p.Gln1292* NI NA 38 P9 c.5461-10TC Unknown NI NA 35, 58 P10 c.1822TA p.Phe608Ile NI NA 23, 41 P11 c.286AG p.Asn96Asp NI NA 43 P12 c.1805GA p.Arg602Gln c.4462TC p.Cys1488Arg 37, 39, 42-44 P13 c.3874CT p.Gln1292* c.1928TG p.Val643Gly 38, 45 NI, not identified; NA, not applicable. Login to comment 149 ABCA4 p.Arg2030Gln In contrast, in our cohort we defined foveal sparing as profound RPE atrophy that surrounded the fovea by at least 1808 and spared the fovea`s structure and function. This clinical presentation is a rare finding among STGD1 patients, and our strict selection criterion resulted in a small but homogeneous cohort with a consistent phenotype and excluded STGD1 patients with late-onset disease that began with foveal atrophy. Moreover, our definition of foveal sparing is consistent with previously reported cases of foveal sparing in patients with other degenerative diseases.6,8,33,34 Despite the differences between our cohort and the cohort described by Fujinami et al.,26 the visual acuity and electrophysiology findings in their paper are similar to the findings in our study; nevertheless, none of our patients were carriers of the ABCA4 p.Arg2030Gln missense mutation, which was suggested previously to be prevalent among STGD1 patients with foveal sparing.26 The Etiology of Foveal Sparing In our study, screening the ABCA4 gene identified 19 pathogenic mutations that were described previously in STGD1 and/or other ABCA4-associated retinopathies (Table 2)16,23,35-45 ; interestingly, however, foveal sparing was not described in any of the patients who were previously reported to carry these mutations. Login to comment 151 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Cys1488Arg ABCA4 p.Asn96Asp ABCA4 p.Ile1562Thr ABCA4 p.Val643Gly ABCA4 p.Ile1846Thr ABCA4 p.Arg602Gln ABCA4 p.Phe608Ile ABCA4 p.Phe608Ile ABCA4 p.Cys1455Arg ABCA4 Mutations in STGD1 Patients With Foveal Sparing Allele 1 Allele 2 References DNA Variant Effect DNA Variant Effect P1 c.5461-10TC Unknown NI NA 35, 36 P2 c.3113CT p.Ala1038Val c.3874CT p.Gln1292* 16, 37, 38, 58 P3 c.5461-10TC Unknown c.5537TC p.Ile1846Thr 23, 35, 39, 58 P4 c.4363TC p.Cys1455Arg NI NA 40 P5 c.1822TA p.Phe608Ile c.4685TC p.Ile1562Thr 23, 40, 41, 59 P6 c.768GT Splice defect c.3113CT p.Ala1038Val 16, 23, 37 P7 c.5196&#fe;1GT Splice defect NI NA 45, 58 P8 c.3874CT p.Gln1292* NI NA 38 P9 c.5461-10TC Unknown NI NA 35, 58 P10 c.1822TA p.Phe608Ile NI NA 23, 41 P11 c.286AG p.Asn96Asp NI NA 43 P12 c.1805GA p.Arg602Gln c.4462TC p.Cys1488Arg 37, 39, 42-44 P13 c.3874CT p.Gln1292* c.1928TG p.Val643Gly 38, 45 NI, not identified; NA, not applicable. Login to comment 302 ABCA4 p.Asn965Ser Rosenberg T, Klie F, Garred P, Schwartz M. N965S is a common ABCA4 variant in Stargardt-related retinopathies in the Danish population. Login to comment