Abstract
De novo variants in the myelin regulatory factor (MYRF), a transcription factor involved in the differentiation of oligodendrocytes, have been linked recently to the cardiac and urogenital syndrome, while familiar variants are associated with nanophthalmos. Here, we report for the first time on a patient with a de novo stop-gain variant in MYRF (p.Q838*) associated with Scimitar syndrome, 46,XY partial gonadal dysgenesis (GD) and severe hyperopia. Since variants in MYRF have been described in both 46,XX and 46,XY GD, we assumed a role of MYRF in the early development of the bipotential gonad. We used publicly available single cell sequencing data of human testis and ovary from different developmental stages and analysed them for MYRF expression. We identified MYRF expression in the subset of coelomic epithelial cells at stages of gonadal ridge development in 46,XX and 46,XY individuals. Differential gene expression analysis revealed significantly upregulated genes. Within these, we identified CITED2 as a gene containing a MYRF binding site. It has been shown that Cited2−/− mice have gonadal defects in both testis and ovary differentiation, as well as defects in heart development and establishment of the left–right axis. This makes MYRF a potential candidate as an early regulator of gonadal and heart development via upregulation of the transcriptional cofactor CITED2.
| Original language | English |
|---|---|
| Article number | 4858 |
| Journal | Journal of Clinical Medicine |
| Volume | 11 |
| Issue number | 16 |
| ISSN | 2077-0383 |
| DOIs | |
| Publication status | Published - 08.2022 |
Funding
V.C.-S., F.O., A.K. and H.B. acknowledge computational support from the OMICS compute cluster at the University of Lübeck. This work was funded by financial support from Bundesministerium für Bildung und Forschung BMBF (01DQ17004) and Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 22167- 390884018) and Bundesministerium für Gesundheit (BMG). V.C.-S. and O.H. have received funding by the German Ministry of Health (grant No. 2519FSB503) for the project “Standardized and centred care for DSD over the lifespan (DSDCare)”. H.F.-S. received a scholarship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2020/13421-8) and by the Alexander von Humboldt Fellowship. M.A.-S. received a DAAD scholarship within the German Egyptian Research Long-term Scholarship (GERLS) Programme, 2019, No. 57460069. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
DFG Research Classification Scheme
- 2.22-03 Human Genetics
