Extremely hypomorphic and severe deep intronic variants in the <i>ABCA4</i> locus result in varying Stargardt disease phenotypes.

ABSTRACT: Autosomal recessive Stargardt disease (STGD1, MIM 248200) is caused by mutations in the ABCA4 gene. Complete sequencing of the ABCA4 locus in STGD1 patients identifies two expected disease-causing alleles in ∼75% of patients and only one mutation in ∼15% of patients. Recently, many possibly pathogenic variants in deep intronic sequences of ABCA4 have been identified in the latter group. We extended our analyses of deep intronic ABCA4 variants and determined that one of these, c.4253+43G>A (rs61754045), is present in 29/1155 (2.6%) of STGD1 patients. The variant is found at statistically significantly higher frequency in patients with only one pathogenic ABCA4 allele, 23/160 (14.38%), MAF = 0.072, compared to MAF = 0.013 in all STGD1 cases and MAF = 0.006

SUBMITTER: Zernant J 

PROVIDER: S-EPMC6071568 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature