| First Author | Jia W | Year | 2024 |
| Journal | Hum Genet | Volume | 143 |
| Issue | 11 | Pages | 1281-1291 |
| PubMed ID | 39110251 | Mgi Jnum | J:359112 |
| Mgi Id | MGI:7778479 | Doi | 10.1007/s00439-024-02697-8 |
| Citation | Jia W, et al. (2024) GBF1 deficiency causes cataracts in human and mouse. Hum Genet 143(11):1281-1291 |
| abstractText | Any opacification of the lens can be defined as cataracts, and lens epithelium cells play a crucial role in guaranteeing lens transparency by maintaining its homeostasis. Although several causative genes of congenital cataracts have been reported, the mechanisms underlying lens opacity remain unclear. In this study, a large family with congenital cataracts was collected and genetic analysis revealed a pathological mutation (c.3857 C > T, p.T1287I) in the GBF1 gene; all affected individuals in the family carried this heterozygous mutation, while unaffected family members did not. Functional studies in human lens epithelium cell line revealed that this mutation led to a reduction in GBF1 protein levels. Knockdown of endogenous GBF1 activated XBP1s in the unfolded protein response signal pathway, and enhances autophagy in an mTOR-independent manner. Heterozygous Gbf1 knockout mice also displayed typic cataract phenotype. Together, our study identified GBF1 as a novel causative gene for congenital cataracts. Additionally, we found that GBF1 deficiency activates the unfolded protein response and leads to enhanced autophagy, which may contribute to lens opacity. |
