title: Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita.
abstract: OBJECTIVE
  To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder.
  
  
  METHODS
  We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels.
  
  
  RESULTS
  DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution.
  
  
  CONCLUSIONS
  A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease.
authors.affiliation: Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Rafael Machado
authors.initials: RM
authors.lastname: Mantovani
authors.forename: Isabela Leite
authors.initials: IL
authors.lastname: Pezzuti
authors.forename: Vera Maria Alves
authors.initials: VM
authors.lastname: Dias
authors.forename: Ivani Novato
authors.initials: IN
authors.lastname: Silva
mesh_terms: D000224:Addison Disease / Q000235:genetics*; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D002648:Child; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human