A novel pathogenic RHOA variant in a patient with patterned cutaneous hypopigmentation associated with extracutaneous findings

Abstract

Hypomelanosis of Ito was first described by Minor Ito in 1952 in a 22-year-old woman with linear symmetric hypopigmentation of her trunk and arms. 1 Over the years, hypomelanosis of Ito became an umbrella term referring to cutaneous hypopigmentation along Blaschko's lines, presenting with or without associated extracutaneous findings in various systems, particularly neurological, skeletal, and ophthalmological. 2 Diagnostic criteria have been proposed by Ruiz-Maldonado and al. in 1992, 3 but no consensus or formal definition has been adopted to this day. Unjustified investigations for the patient and unnecessary stress for the parents could be avoided with a better delineation of syndromic patterned hypopigmentation.Identification of postzygotic variants in vascular anomalies, such as port-wine stains and Sturge-Weber syndrome (GNAQ), and hamartomatous skin disorders, such as sebaceous nevi and Schimmelpenning syndrome (KRAS and HRAS), 4,5 stimulated the search for the genetic basis of pigmentary mosaicism. To this day, three distinct mosaic hypopigmentation syndromes 6-8 have been identified with postzygotic variants in MTOR, TFE3, and RHOA genes. | C A S E REP ORTA girl born at term by spontaneous delivery to non-consanguineous French-Canadian (Caucasian) parents after an uneventful pregnancy

Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling

“…In the central nervous system, the GTPase RhoA/Rho1 maintains the integrity of adherens junctions by retaining the organization and number of spinal cord neuroepithelium (neural stem cells) (83). Consistent with this, inactivating variants of human RHOA cause a neuroectodermal syndrome with linear hypopigmentation (84,85). These reports suggest that Gq-RhoA signaling may have a general role in promoting cell proliferation during development.…”

Astrocytes control quiescent NSC reactivation via GPCR signaling–mediated F-actin remodeling

“…In the central nervous system, the GTPase RhoA/Rho1 maintains the integrity of adherens junctions by retaining the organization and number of spinal cord neuroepithelium (NSCs) (85). Consistent with this, inactivating variants of human RHOA cause a neuroectodermal syndrome with linear hypopigmentation (86,87). These reports suggest that Gα q -RhoA signaling may have a general role in promoting cell proliferation during development.…”