Mosaic Activating Mutations in GNA11 and GNAQ Are Associated with Phakomatosis Pigmentovascularis and Extensive Dermal Melanocytosis.

Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) are usually localized and transient, but they can be extensive, permanent, and associated with extracutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of phakomatosis pigmentovascularis, a group of syndromes associated with neurovascular, ophthalmological, overgrowth, and malignant complications. Here, we discover that extensive dermal melanocytosis and phakomatosis pigmentovascularis are associated with activating mutations in GNA11 and GNAQ, genes that encode Gα subunits of heterotrimeric G proteins. The mutations were detected at very low levels in affected tissues but were undetectable in the blood, indicating that these conditions are postzygotic mosaic disorders. In vitro expression of mutant GNA11(R183C) and GNA11(Q209L) in human cell lines demonstrated activation of the downstream p38 MAPK signaling pathway and the p38, JNK, and ERK pathways, respectively. Transgenic mosaic zebrafish models expressing mutant GNA11(R183C) under promoter mitfa developed extensive dermal melanocytosis recapitulating the human phenotype. Phakomatosis pigmentovascularis and extensive dermal melanocytosis are therefore diagnoses in the group of mosaic heterotrimeric G-protein disorders, joining McCune-Albright and Sturge-Weber syndromes. These findings will allow accurate clinical and molecular diagnosis of this subset of common birthmarks, thereby identifying infants at risk for serious complications, and provide novel therapeutic opportunities

Brown–McLean syndrome: the role of iridodonesis

Yanin Suwan, Chaiwat Teekhasaenee, Kaevalin Lekhanont, Wasu Supakontanasan Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Purpose: The aim of this study was to report a case series of Brown–McLean syndrome (BMS).Methods: The charts of 28 patients with BMS at Ramathibodi and Rutnin Hospital from 1981 to 2015 were reviewed.Results: BMS is a rare condition with corneal edema involving the peripheral cornea with orange-brown pigment deposition underlying the edematous area. The edema typically starts inferiorly and advances circumferentially to superior cornea. Central cornea remains clear in most patients. We report 28 patients with BMS that occurred either spontaneously or after various intraocular procedures. Ultrasound biomicroscopy was performed to demonstrate the iridocorneal relationship.Conclusion: Iridocorneal relationship from the ultrasound biomicroscopy study in four patients did not support previous hypothesis about the role of iridodonesis impact on corneal endothelium. Patients with BMS can rarely progress to corneal decompensation; however, they should be periodically monitored and made aware of early clinical signs of their complications. Keywords: Brown–McLean syndrome, peripheral corneal edema, marginal corneal edema, corneal decompensatio

Epstein–Barr virus-associated iris smooth muscle tumor with epithelioid morphology in AIDS patients: a case report

Yanin Suwan,1 Duangnate Rojanaporn,1 Chaiwat Teekhasaenee,1 Somboon Keelawat2 1Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 2Department of Pathology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand Importance: Report of an acquired immunodeficiency syndrome (AIDS) patient with Epstein–Barr virus (EBV)-associated iris smooth muscle tumor. Observations: A 14-year-old African American female diagnosed with AIDS developed a painless iris mass in the right eye for 10 months. Iridocyclectomy was performed, and the pathology indicated EBV-associated iris smooth muscle tumor with epithelioid morphology. Immunohistochemical stains and in situ hybridization for EBV-encoded ribonucleic acid are very useful diagnostic tools for definite diagnosis. At 14-month follow-up, the patient did not have any tumor recurrence. Conclusion: This is the case report of EBV-associated iris smooth muscle tumor in a person diagnosed with AIDS with a unique epithelioid morphologic feature. Keywords: human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), iris tumor, Epstein–Barr virus, smooth muscle tumor, leiomyosarcoma&nbsp