| First Author | Tan S | Year | 2019 |
| Journal | Blood | Volume | 134 |
| Issue | 3 | Pages | 277-290 |
| PubMed ID | 31151987 | Mgi Jnum | J:280074 |
| Mgi Id | MGI:6364265 | Doi | 10.1182/blood.2018893404 |
| Citation | Tan S, et al. (2019) EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome. Blood 134(3):277-290 |
| abstractText | Shwachman-Diamond syndrome (SDS) is a recessive disorder typified by bone marrow failure and predisposition to hematological malignancies. SDS is predominantly caused by deficiency of the allosteric regulator Shwachman-Bodian-Diamond syndrome that cooperates with elongation factor-like GTPase 1 (EFL1) to catalyze release of the ribosome antiassociation factor eIF6 and activate translation. Here, we report biallelic mutations in EFL1 in 3 unrelated individuals with clinical features of SDS. Cellular defects in these individuals include impaired ribosomal subunit joining and attenuated global protein translation as a consequence of defective eIF6 eviction. In mice, Efl1 deficiency recapitulates key aspects of the SDS phenotype. By identifying biallelic EFL1 mutations in SDS, we define this leukemia predisposition disorder as a ribosomopathy that is caused by corruption of a fundamental, conserved mechanism, which licenses entry of the large ribosomal subunit into translation. |
