ABCMdb

PMID: 16682602

Fingert JH, Eliason DA, Phillips NC, Lotery AJ, Sheffield VC, Stone EM
Case of Stargardt disease caused by uniparental isodisomy.
Arch Ophthalmol. 2006 May;124(5):744-5., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu Goldmann vi- sualfieldsconfirmedbilateralcentral scotomas,andastandardelectroreti- nogramwasnormal.Thepatientwas tested for ABCA4 mutations using standardmethods6 andwasfoundto behomozygousforanABCA4muta- tion of proline to leucine at position 1380 (P1380L). Login to comment 3 ABCA4 p.Pro1380Leu Interestingly, only the patient`s father is a carrier of the P1380L mutation. Login to comment 6 ABCA4 p.Pro1380Leu Quantitative polymer- asechainreactionexperimentscon- firmed that the patient was truly homozygous for P1380L (data not shown),suggestingthatbothcopies of this mutation were paternally inherited due to uniparental disomy. Login to comment 13 ABCA4 p.Pro1380Leu Recessive alleles on the involved chromosome in uniparental disomy may become homozygous in offspring.Consequently,uniparentaldi- somy may result in expression of a recessive disease inherited from only 1parent.Thisnon-Mendelianmecha- nism of disease inheritance has been observed in rod monochromacy,7 retinitis pigmentosa,8-11 and Leber congenital amaurosis.10 We investigated whether the patient inherited both P1380L alleles of the ABCA4 gene from her father by genotyping the patient and her family at 24 short tandem repeat polymorphism genetic markers distributed across chromosome 1 using standard techniques12 (Figure 3). Login to comment 17 ABCA4 p.Pro1380Leu These data suggest that the patient is homozygous for the P1380L ABCA4 mutation as a consequence of inheriting 2 identical copies of chromosome 1 from her father (uniparental paternal isodisomy). Login to comment 24 ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu Wt/P1380L Wt/Wt P1380/WtP1380L/P1380L Figure 2. Login to comment 26 ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu The proband (filled symbol) has Stargardt disease and is homozygous for the P1380L mutation (mutation of proline to leucine at position 1380) in ABCA4. Login to comment 99 ABCA4 p.Pro1380Leu D1S468 D1S1612* D1S1635* D1S552 D1S3721* D1S188* D1S2868* D1S2849* D1S406* D1S2779* ABCA4 (P1380L) D1S1587 Centromere D1S1671* D1S3723* D1S305* D1S1595* D1S1699 D1S1677 D1S2790* D1S1660* D1S1726 D1S1632 124 FO8 D1S179* D1S1609* 4.22 16.22 23.35 45.33 72.59 126.16 126.16 126.16 126.16 126.16 128.73 134.20 140.39 159.32 161.05 170.84 175.62 190.98 212.44 214.08 214.08 226.16 252.12 274.53 2 2 2 1 3 2 1 2 1 1 L 2 ߦ 1 4 1 1 1 2 4 1 2 1 2 3 2 2 2 2 1 3 2 1 2 1 1 L 2 ߦ 1 4 1 1 1 2 4 1 2 1 2 3 2 Patient Mother 1 1 1 1 2 3 2 1 3 2 P 1 ߦ 2 1 2 2 1 2 1 2 2 1 2 1 1 2 3 3 1 4 4 3 3 4 2 P 2 ߦ 2 2 2 3 1 3 2 3 3 3 3 2 3 Father Sister 2 2 2 1 1 1 1 2 1 1 P 2 ߦ 1 3 1 1 1 2 3 1 1 1 1 3 2 2 2 3 2 3 2 2 3 2 2 L 2 ߦ 1 4 2 1 2 1 4 1 2 2 2 3 3 1 1 1 1 1 2 1 1 1 1 P 2 ߦ 1 1 1 1 1 2 1 1 1 2 1 2 1 2 2 3 2 4 4 3 2 4 2 L 2 ߦ 2 4 2 3 1 3 4 3 2 3 3 3 3 Marker Locus, cM Figure 3. Login to comment 101 ABCA4 p.Pro1380Leu D1S468 D1S1612* D1S1635* D1S552 D1S3721* D1S188* D1S2868* D1S2849* D1S406* D1S2779* ABCA4 (P1380L) D1S1587 Centromere D1S1671* D1S3723* D1S305* D1S1595* D1S1699 D1S1677 D1S2790* D1S1660* D1S1726 D1S1632 124 FO8 D1S179* D1S1609* 4.22 16.22 23.35 45.33 72.59 126.16 126.16 126.16 126.16 126.16 128.73 134.20 140.39 159.32 161.05 170.84 175.62 190.98 212.44 214.08 214.08 226.16 252.12 274.53 2 2 2 1 3 2 1 2 1 1 L 2 • 1 4 1 1 1 2 4 1 2 1 2 3 2 2 2 2 1 3 2 1 2 1 1 L 2 • 1 4 1 1 1 2 4 1 2 1 2 3 2 Patient Mother 1 1 1 1 2 3 2 1 3 2 P 1 • 2 1 2 2 1 2 1 2 2 1 2 1 1 2 3 3 1 4 4 3 3 4 2 P 2 • 2 2 2 3 1 3 2 3 3 3 3 2 3 Father Sister 2 2 2 1 1 1 1 2 1 1 P 2 • 1 3 1 1 1 2 3 1 1 1 1 3 2 2 2 3 2 3 2 2 3 2 2 L 2 • 1 4 2 1 2 1 4 1 2 2 2 3 3 1 1 1 1 1 2 1 1 1 1 P 2 • 1 1 1 1 1 2 1 1 1 2 1 2 1 2 2 3 2 4 4 3 2 4 2 L 2 • 2 4 2 3 1 3 4 3 2 3 3 3 3 Marker Locus, cM Figure 3. Login to comment