case_images: PMC2553007_01
case_images: Ophthalmological findings. A: Fundus photograph of the patient's left eye shows macular yellow flecks characteristic of Stargardt macular dystrophy. B: Angiofluoresceingraphy (AFG) shows silent choroid and atrophic retinal pigment epithelium at the macular area.
case_images: mv-v13-96-f1.jpg
case_images: PMC2553007_01_mv-v13-96-f1.jpg
case_images: f1
case_images: At the age of 35, her visual acuity was 100/200, biomicroscopy was normal and funduscopy revealed yellowish flecks at the macula (Figure 1A). Angiofluoresceingraphy (AFG) showed silent choroid areas and hyperfluorescent dots at the perifoveal retina, resembling little defects at the RPE (Figure 1B).
case_images: PMC2553007_02
case_images: The DNA sequence of ABCA4 codons 1126 to 1132, in the index patient and both parents. The patient (02/725) shows a homozygous pattern for the missense p.Arg1129Leu mutation. Her father (02/724) presents a heterozygous pattern, while her mother (02/726) shows a homozygous wild-type sequence.
case_images: mv-v13-96-f2.jpg
case_images: PMC2553007_02_mv-v13-96-f2.jpg
case_images: f2
case_images: The R1129L mutation was present in a heterozygous pattern in her unaffected father, but interestingly her mother did not harbor this change (Figure 2).
case_images: Pedigree showing the pattern of the 32 genetic markers used for chromosome 1 in the proband and in her parents. Patient's haplotype demonstrates that 5 markers for 1p, from D1S435 to D1S2664 (black bar), were homozygous and derived from one paternal chromosomal homolog. We concluded that paternal partial isodisomy was present, with breakpoints between 1p22.3 (D1S167-D1S435) and 1p22.1 (D1S2664-D1S2793). Markers D1S2793 and D1S206 could also be involved in the isodisomy, but were not informative (striped bar). Markers located on the short arm (excluding the isodisomic region), on the centromeric region, and on the distal region from the long arm (shown in brackets) clearly indicate normal maternal and paternal segregation. For the remaining markers along 1q, we could not distinguish between normal segregation or (partial) maternal heterodisomy. The location of the genetic markers, placed on the physical and cytogenetic maps of chromosome 1, was established according to the information contained in the NCBI database.
case_images: mv-v13-96-f3.jpg
case_images: PMC2553007_02_mv-v13-96-f3.jpg
case_images: f3
case_images: For the remaining markers spanning both arms of chromosome 1, we could not distinguish between normal biparental segregation or maternal uniparental heterodisomy (Figure 3).
case_images: Multiplex ligation-dependent probe amplification (MLPA) of ABCA4 exons. Multiplex ligation-dependent probe amplification (MLPA) electropherograms from the proband and one control sample. Shaded peaks represent ABCA4 exon probes, normal peaks represent synthetic probes. Every probe presented a normal amplification pattern, suggesting normal dosage for both copies of ABCA4. Therefore, the possibility of a microdeletion was ruled out.
case_images: mv-v13-96-f4.jpg
case_images: PMC2553007_02_mv-v13-96-f4.jpg
case_images: f4
case_images: This result firmly confirmed that both ABCA4 alleles were present in our patient (Figure 4).