[HTML][HTML] Deep-intronic ABCA4 variants explain missing heritability in Stargardt disease and allow correction of splice defects by antisense oligonucleotides
Purpose Using exome sequencing, the underlying variants in many persons with autosomal
recessive diseases remain undetected. We explored autosomal recessive Stargardt disease
(STGD1) as a model to identify the missing heritability. Methods Sequencing of ABCA4 was
performed in 8 STGD1 cases with one variant and p. Asn1868Ile in trans, 25 cases with one
variant, and 3 cases with no ABCA4 variant. The effect of intronic variants was analyzed
using in vitro splice assays in HEK293T cells and patient-derived fibroblasts. Antisense …
recessive diseases remain undetected. We explored autosomal recessive Stargardt disease
(STGD1) as a model to identify the missing heritability. Methods Sequencing of ABCA4 was
performed in 8 STGD1 cases with one variant and p. Asn1868Ile in trans, 25 cases with one
variant, and 3 cases with no ABCA4 variant. The effect of intronic variants was analyzed
using in vitro splice assays in HEK293T cells and patient-derived fibroblasts. Antisense …