| First Author | Tobias ES | Year | 2024 |
| Journal | Endocrine | Volume | 84 |
| Issue | 2 | Pages | 345-349 |
| PubMed ID | 38400880 | Mgi Jnum | J:351615 |
| Mgi Id | MGI:7702356 | Doi | 10.1007/s12020-024-03701-x |
| Citation | Tobias ES, et al. (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine 84(2):345-349 |
| abstractText | PURPOSE: Disorders/differences of sex development (DSD) result from variants in many different human genes but, frequently, have no detectable molecular cause. METHODS: Detailed clinical and genetic phenotyping was conducted on a family with three children. A Sec31a animal model and functional studies were used to investigate the significance of the findings. RESULTS: By trio whole-exome DNA sequencing we detected a heterozygous de novo nonsense SEC31A variant, in three children of healthy non-consanguineous parents. The children had different combinations of disorders that included complete gonadal dysgenesis and multiple pituitary hormone deficiency. SEC31A encodes a component of the COPII coat protein complex, necessary for intracellular anterograde vesicle-mediated transport between the endoplasmic reticulum (ER) and Golgi. CRISPR-Cas9 targeted knockout of the orthologous Sec31a gene region resulted in early embryonic lethality in homozygous mice. mRNA expression of ER-stress genes ATF4 and CHOP was increased in the children, suggesting defective protein transport. The pLI score of the gene, from gnomAD data, is 0.02. CONCLUSIONS: SEC31A might underlie a previously unrecognised clinical syndrome comprising gonadal dysgenesis, multiple pituitary hormone deficiencies, dysmorphic features and developmental delay. However, a variant that remains undetected, in a different gene, may alternatively be causal in this family. |
