UNASSIGNED: To highlight the challenges in diagnosing 46, XY disorder of sex development related to MYRF mutation.
UNASSIGNED: We present an unusual case of a 12-year-old female child came for enlargement of clitoris and initially diagnosed as partial androgen insensitivity syndrome (AIS).
UNASSIGNED: On examination, the patient\'s vulva was found virilized with 3cm-long clitoris. Her peripheral blood karyotype was 46, XY. The ultrasound showed an empty pelvis and hormone results confirmed hyperandrogenism. Therefore, the partial AIS was suspected, but the following whole exon sequencing indicates a pathological missense mutation in MYRF. Further investigation and surgery did not reveal any brain, heart, lung or diaphragm lesions related to MYRF, but only maldeveloped internal genitalia and a persistent urachus. Her serum testosterone dropped to normal after surgical removal of the remaining ipsilateral testis and epididymitis without spermatogenesis as shown by pathology.
UNASSIGNED: Due to the karyotype, hyperandrogenism, empty pelvis but a virilism after puberty, the patient was initially diagnosed as partial AIS. This misleading clinical diagnose will not be verified as the MYRF mutation if without the whole exon sequencing, particularly in the absence of obvious brain, heart, lung and diaphragm lesions as in this case.

HIV-associated neurocognitive disorders (HAND) remain pervasive even with increased efficacy/use of antiretroviral therapies. Opioid use/abuse among HIV + individuals is documented to exacerbate CNS deficits. White matter (WM) alterations, including myelin pallor, and volume/structural alterations detected by diffusion tensor imaging are common observations in HIV + individuals, and studies in non-human primates suggest that WM may harbor virus. Using transgenic mice that express the HIV-1 Tat protein, we examined in vivo effects of 2-6 weeks of Tat and morphine exposure on WM using genomic and biochemical methods. RNA sequencing of striatal tissue at 2 weeks revealed robust changes in mRNAs associated with oligodendrocyte precursor populations and myelin integrity, including those for transferrin, the atypical oligodendrocyte marker N-myc downstream regulated 1 (Ndrg1), and myelin regulatory factor (Myrf/Mrf), an oligodendrocyte-specific transcription factor with a significant role in oligodendrocyte differentiation/maturation. Western blots conducted after 6-weeks exposure in 3 brain regions (striatum, corpus callosum, pre-frontal cortex) revealed regional differences in the effect of Tat and morphine on Myrf levels, and on levels of myelin basic protein (MBP), whose transcription is regulated by Myrf. Responses included individual and interactive effects. Although baseline and post-treatment levels of Myrf and MBP differed between brain regions, post-treatment MBP levels in striatum and pre-frontal cortex were compatible with changes in Myrf activity. Additionally, the Myrf regulatory ubiquitin ligase Fbxw7 was identified as a novel target in our model. These results suggest that Myrf and Fbxw7 contribute to altered myelin gene regulation in HIV.