ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2020) 17 6.7 | DOI: 10.1530/ey.17.6.7


To read the full abstract: Hum Mol Genet. 2019, Jul 15; 28: 2319–29. doi: https://academic.oup.com/hmg/article/28/14/2319/5424416

This study provides evidence that MYRF is important in the development of coelomic endothelial derived cells, and early gonadal development in both males and females. It combines detailed phenotypic assessment of patients and whole genome sequencing with basic biology using single cell gene expression analysis and comprehensive mapping of putative target genes and bioinformatics. The authors conclude that MYRF may be involved in not only in the development of the bipotential gonad but also in the early development of the Mullerian ducts.

MYRF (OMIM 608329; 11q12.2), encoding myelin regulatory factor, is a transcription factor that regulates proliferation and migration of coelomic endothelial derived cells (CEDC); it is essential for the development of multiple organs and plays a role in oligodendrocyte development.

This case–control exome sequencing study identified rare heterozygous truncating variants in MYRF by comparing rare damaging variants in 26 DSD cases with 2625 controls. Three patients with XY karyotype had micro-penis, hypospadias, small testis and cryptorchidism as signs of impaired Sertoli and Leydig cell function. Their laboratory measurements showed low testosterone and AMH and increased gonadotrophins. One patient had congenital diaphragmatic hernia, a defect in the development of pleuroperitoneal folds. In monozygotic twin with XX karyotype, the mutation led to hypoplasia of Müllerian derivatives and ovaries with increased gonadotrophins.

The expression patterns of MYRF in fetal gonads was studied using single-cell RNA sequencing of human male and female gonads. The findings revealed that male fetal gonadal cells express WT1 and AMH markers of Sertoli cell lineage, and NR2F2 was expressed which corresponds to the Leydig cell lineage. The female gonads expressed UPK3B, a marker of coelomic epithelial cells, FOXL2, a granulosa cell marker and NR2F2, a thecal cell lineage marker.

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