Xiaoliang Liu, Yuanyuan Zhang, Bijun Zhang, Haiming Gao, Chuang Qiu
Molecular genetics & genomic medicine 2020 MayCongenital aniridia is a severe ocular abnormality characterized by incomplete formation of the iris and many other ocular complications. Most cases are caused by the paired box 6 (PAX6) gene mutations generating premature termination codons (PTCs). Ophthalmic examination was performed on a Chinese pedigree with congenital aniridia. The mutation was identified by targeted next-generation sequencing. Nonsense suppression therapy was applied on patient-derived lymphocytes. The PAX6 expression was assayed by real-time polymerase chain reaction and Western blot. Complete aniridia was complicated with horizontal nystagmus, contract, foveal hypoplasia, and microphthalmia. A novel heterozygous c.702_703delinsAT (p.Tyr234*) mutation was found in exon 9 of PAX6, generating a PTC at the homeodomain. There were about 50% reductions of both full-length PAX6 protein and PAX6 mRNA in patient-derived lymphocytes, indicating haploinsufficiency due to nonsense-mediated mRNA decay. Ataluren (PTC124) and geneticin (G418) could induce about 30%-40% translational readthrough. Nonsense suppression therapy restored PAX6 protein to about 65%-70% of unaffected family controls. Our data expanded the genetic and phenotypic variations of congenital aniridia, and showed the therapeutic effect of nonsense suppression on this disease using patient-derived cells. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Xiaoliang Liu, Yuanyuan Zhang, Bijun Zhang, Haiming Gao, Chuang Qiu. Nonsense suppression induced readthrough of a novel PAX6 mutation in patient-derived cells of congenital aniridia. Molecular genetics & genomic medicine. 2020 May;8(5):e1198
PMID: 32125788
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