Long-term clinical data and molecular defects in the STAR gene in five Greek patients

Abstract

ContextSteroidogenic acute regulatory (STAR) gene mutations lead to adrenal and gonadal failure. Interesting, though as yet unexplained, features are the formation of ovarian cysts and the potential presence of CNS findings.ObjectiveTo report biochemical, genetic, and long-term clinical data in five Greek patients from four different families withSTARgene defects (three 46,XX and two 46,XY).Methods and resultsAll patients presented in early infancy with adrenal insufficiency. TheSTARgene mutation c.834del11bp, detected in three of our patients, completely alters the carboxyl end of the STAR protein and has not thus far been described in other population groups. These three patients belong to three separate families, possibly genetically related, as they live in different villages located in a small region of a Greek island. However, their interrelationship has not been proven. A second mutation, p.W250X, detected in our fourth family, was previously described only in two Serbian patients. Ovarian cysts were detected ultrasonographically in our 46,XX patients and seemed to respond to a low dose of a contraceptive. The histology of an excised ovarian cyst was diagnosed as a corpus luteum (CL) cyst. In two out of the four patients who had undergone brain magnetic resonance imaging, asymptomatic Chiari-1 malformation was observed.ConclusionsThe occurrence ofSTARgene mutation c.834del11bp in three families living in a restricted geographic region could indicate either a founder effect or simply reflect a spread of this defect in a highly related population. The ovarian histological findings suggest that ovarian cysts detected ultrasonographically in 46,XX individuals withSTARgene defects may be CL cysts. The Chiari-1 malformation in two of our patients may be part of theSTARgene mutation phenotype. Nevertheless, more data are needed to confirm or disprove the existence of specific CNS pathology in patients withSTARgene mutations.