In branch A, 5 patients displayed STGD with initially 3 different phenotypes .
In branch B, 2 patients III8 and III10 presented initial phenotype 4 STGD (Stargardt fundus flavimaculatus, later age of onset) with central atrophy, yellow-white dots, macular atrophy, hyperfluorescent atrophic spots, and silent choroid.
To date, large genomic rearrangements account for a minor portion of STGD disease alleles.
The buildup of lipofuscin is toxic and causes progressive vision loss in subjects with STGD macular degeneration.
We found pathogenic mutations in 16 genes, with the most recurrent being ABCA4 for STGD and USH2A for RP/USH patients.
The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients with well-defined clinical diagnosis, where the number of known genes associated with each disease is relatively limited.
For STGD patients, genetic diagnosis was achieved in 11 out of 14 (78.5% of the cases).
More specifically, among the different clinical phenotypes, the highest detection rates were achieved for BMD, LCA, USH, and STGD patients, in whom the genetic test clearly confirmed the clinical diagnoses (Table 2).
Mixing of samples with each other instead of with a wild-type sample was feasible because of the scarcity of homozygous mutated STGD patients [<3% in our population (4)], which makes the probability of mixing two samples homozygous for the same mutation low enough to be negligible.
Additionally, DHPLC profiling singled out the presence of the mutations D108V (323A>T) in exon 4, V767D (2300T>A) in exon 15 (7), R2030Q (6089G>A) in exon 44 (8), and 6817-1G>A and a 3329-25G>A polymorphism in five STGD patients that DG-DGGE had failed to detect.
In fact, retrospective DHPLC analysis of samples from 23 STGD patients not only detected all sequence variations previously identified by DG-DGGE but also revealed five additional changes that DG-DGGE had missed.
The lack of a rapid, automated scanning methodology for the detection of unknown sequence alterations has meant that general molecular testing for STGD has previously been performed by only a very few, specialized centers.