期刊
KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
卷 237, 期 3, 页码 267-274出版社
GEORG THIEME VERLAG KG
DOI: 10.1055/a-1057-9939
关键词
Stargardt disease; variants; splice defects; deep-intronic variants; reduced penetrance
资金
- RetinaUK [GR591]
- Rotterdamse Stichting Blindenbelangen
- Stichting Blindenhulp
- Stichting tot Verbetering van het Lot der Blinden
- Landelijke Stichting voor Blinden en Slechtzienden
- Macula Degeneratie fonds
- Stichting Blinden-Penning
Autosomal recessive Stargardt disease ( STGD1) is associated with variants in the ABCA4 gene. The phenotypes range from early-onset STGD1, that clinically resembles severe cone- rod dystrophy, to intermediate STGD1 and late-onset STGD1. These different phenotypes can be correlated with different combinations of ABCA4 variants which can be classified according to their degree of severity. A significant fraction of STGD1 cases, particularly late-onset STGD1 cases, were shown to carry only a single ABCA4 variant. A frequent coding variant (p.Asn1868Ile) was recently identified which - in combination with a severe ABCA4 variant - is generally associated with late-onset STGD1. In addition, an increasing number of rare deep-intronic variants have been found and some of these are also associated with late-onset STGD1. The effect of these and other variants on ABCA4 RNA was tested using in vitro assays in human kidney cells using specially designed midigenes. With stem cells and photoreceptor progenitor cells derived from patient skin or blood cells, retina-specific splice defects can be assessed. With expert clinical examination to distinguish STGD1 cases from other maculopathies, as well as in-depth genomics and transcriptomics data, it is now possible to identify both mutant ABCA4 alleles in > 95% of cases.
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