title: Long-term clinical data and molecular defects in the STAR gene in five Greek patients.
abstract: BACKGROUND
  Steroidogenic 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.
  
  
  OBJECTIVE
  To report biochemical, genetic, and long-term clinical data in five Greek patients from four different families with STAR gene defects (three 46,XX and two 46,XY).
  
  
  RESULTS
  All patients presented in early infancy with adrenal insufficiency. The STAR gene 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.
  
  
  CONCLUSIONS
  The occurrence of STAR gene 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 with STAR gene defects may be CL cysts. The Chiari-1 malformation in two of our patients may be part of the STAR gene mutation phenotype. Nevertheless, more data are needed to confirm or disprove the existence of specific CNS pathology in patients with STAR gene mutations.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Agia Sophia Children's Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: Amalia
authors.initials: A
authors.lastname: Sertedaki
authors.forename: Maria
authors.initials: M
authors.lastname: Dracopoulou
authors.forename: Antonis
authors.initials: A
authors.lastname: Voutetakis
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Stefanaki
authors.forename: Dimitra
authors.initials: D
authors.lastname: Rontogianni
authors.forename: Alexandra-Maria
authors.initials: AM
authors.lastname: Magiakou
authors.forename: Christina
authors.initials: C
authors.lastname: Kanaka-Gantenbein
authors.forename: George
authors.initials: G
authors.lastname: Chrousos
authors.forename: Catherine
authors.initials: C
authors.lastname: Dacou-Voutetakis
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D000309:Adrenal Insufficiency / Q000151:congenital / Q000209:etiology; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D006115:Greece; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008521:Mediterranean Islands; D009154:Mutation; D010048:Ovarian Cysts / Q000209:etiology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein