Purpose: Mutations in the ABCA4 gene are heterogeneous and somewhat ethnic specific and can result in autosomal recessive Stargardt disease (STGD1), cone or cone-rod dystrophy (CRD), and retinitis pigmentosa. The objective of this study was to determine the ABCA4 mutation detection rate and mutation spectrum in a cohort of Chinese patients with STGD1 or CRD and describe the clinical features of the patients with ABCA4 mutations.
Methods: A total of 161 probands were recruited for genetic analysis; these included 96 patients diagnosed with STGD1 and 65 individuals with CRD. All probands underwent ophthalmic examinations. All coding exons and exon-intron boundaries of the ABCA4 gene were screened for mutations by PCR-based DNA sequencing, followed by analyses for pathogenicity by in silico programs.
Results: We found at least two disease-causing ABCA4 alleles in 102 unrelated patients (63.4%), one disease-causing allele in 16 patients (9.9%), and no disease-causing allele in 43 affected individuals (26.7%), giving an overall mutation detection rate of 73.3% (118/161). In total, 136 disease-causing variants of the ABCA4 gene, including 85 novel ones, were identified. The identified mutations included 77 (57.0%) missense, 19 (14.1%) nonsense, 23 (17.0%) splicing effect, and 16 (11.9%) frameshift small insertion or deletion mutations. The most frequent mutation in this cohort was c.2424C>G p.Y808X, representing 4.7% of all screened alleles (15/322).
Conclusions: The mutation spectrum of the ABCA4 gene in Chinese patients is quite different from that for Caucasian patients. The establishment of the mutation profile will facilitate ABCA4 screening and risk evaluation for Chinese patients with STGD1.