title: Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1.
abstract: BACKGROUND
  X-linked adrenal hypoplasia congenita (AHC) is caused by NR0B1 (DAX1) gene mutations. Affected male children suffer from adrenal insufficiency, leading to a salt-wasting crisis in early infancy and hypogonadotropic hypogonadism in adulthood.
  
  
  OBJECTIVE
  To characterize clinically and at the molecular level a cohort of Spanish patients with AHC.
  
  
  METHODS
  Nine boys (from five families) with AHC were screened for NR0B1 mutations. Clinical and endocrine evaluations were recorded.
  
  
  RESULTS
  NR0B1 gene mutations were found in all analyzed patients, one of them being novel (p.Gln305*). One patient presented with preserved hypothalamic-pituitary-gonadal axis. Salt-wasting episodes, delayed puberty, and hypogonadotropic hypogonadism were common, although no association was observed between AHC phenotype and genetic mutations. None of the patients has had descendants.
  
  
  CONCLUSIONS
  AHC phenotype cannot be predicted based on genetic results as there is no definite genotype-phenotype relationship, including intrafamilial variability. Nevertheless, genetic testing for NR0B1 mutations is indicated if there is a suspicion of an X-linked adrenal insufficiency in order to proceed with the appropriate therapy and genetic counseling.
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez Estévez
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pérez-Nanclares
authors.forename: Joaquin
authors.initials: J
authors.lastname: Fernández-Toral
authors.forename: Francisco
authors.identifier: http://orcid.org/0000-0003-2690-8677
authors.initials: F
authors.lastname: Rivas-Crespo
authors.forename: Juan P
authors.initials: JP
authors.lastname: López-Siguero
authors.forename: Ignacio
authors.initials: I
authors.lastname: Díez
authors.forename: Gema
authors.initials: G
authors.lastname: Grau
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000097:blood / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood; D002648:Child; D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000097:blood / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000075262:Hypoadrenocorticism, Familial; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone