Heterozygous Deep-Intronic Variants and Deletions in ABCA4 in Persons with Retinal Dystrophies and One Exonic ABCA4 Variant

NM Bax, R Sangermano, S Roosing, Alberta Thiadens, LH Hoefsloot, LI van den Born, M Phan, BJ Klevering, C Westeneng-van Haaften, TA Braun, MN Zonneveld-Vrieling, I de Wijs, M Mutlu, EM Stone, AI Hollander, Caroline Klaver, C Hoyng, FPM Cremers

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62 Citations (Scopus)


Variants in ABCA4 are responsible for autosomal-recessive Stargardt disease and cone-rod dystrophy. Sequence analysis of ABCA4 exons previously revealed one causative variant in each of 45 probands. To identify the missing variants in these cases, we performed multiplex ligation-dependent probe amplification-based deletion scanning of ABCA4. In addition, we sequenced the promoter region, fragments containing five deep-intronic splice variants, and 15 deep-intronic regions containing weak splice sites. Heterozygous deletions spanning ABCA4 exon 5 or exons 20-22 were found in two probands, heterozygous deep-intronic variants were identified in six probands, and a deep-intronic variant was found together with an exon 20-22 deletion in one proband. Based on ophthalmologic findings and characteristics of the identified exonic variants present in trans, the deep-intronic variants V1 and V4 were predicted to be relatively mild and severe, respectively. These findings are important for proper genetic counseling and for the development of variant-specific therapies.
Original languageUndefined/Unknown
Pages (from-to)43-47
Number of pages5
JournalHuman Mutation
Issue number1
Publication statusPublished - 2015

Research programs

  • EMC NIHES-01-64-02
  • EMC OR-01-60-01

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