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We studied a patient with severe unilateral microphthalmia who had a 2.7 Mb deletion at chromosome 18q22.1 that was inherited from his mother. In-situ hybridization showed that one of the deleted genes, TMX3, was expressed in the retinal neuroepithelium and lens epithelium in the developing murine eye. We re-sequenced TMX3 in 162 patients with anophthalmia or microphthalmia, and found two missense substitutions in unrelated patients: c.116G>A, predicting p.Arg39Gln, in a male with unilateral microphthalmia and retinal coloboma, and c.322G>A, predicting p.Asp108Asn, in a female with unilateral microphthalmia and severe micrognathia. We used two antisense morpholinos targeted against the zebrafish TMX3 orthologue, zgc:110025, to examine the effects of reduced gene expression in eye development. We noted that the morphant larvae resulting from both morpholinos had significantly smaller eye sizes and reduced labeling with islet-1 antibody directed against retinal ganglion cells at 2 days post fertilization. Co-injection of human wild type TMX3 mRNA rescued the small eye phenotype obtained with both morpholinos, whereas co-injection of human TMX3(p.Arg39Gln) mutant mRNA, analogous to the mutation in the patient with microphthalmia and coloboma, did not rescue the small eye phenotype. Our results show that haploinsufficiency for TMX3 results in a small eye phenotype and represents a novel genetic cause of microphthalmia and coloboma. Future experiments to determine if other thioredoxins are important in eye morphogenesis and to clarify the mechanism of function of TMX3 in eye development are warranted.","is_dataset_classified":null,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20485507","pmcid":"PMC2868029","openalex_id":"https://openalex.org/W2164628276","authors":[],"funders":[{"funder_name":"PHS HHS","grant_id":"5R03 HDO49411-02","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"K08 HD053476","title":null},{"funder_name":"NEI NIH HHS","grant_id":"P30 EY002162","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"K08HD053476-01A1","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"R03 HD049411","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"UL1 RR024131","title":null},{"funder_name":"NEI NIH 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