title: A novel mutation in DAX1 gene causing different phenotypes in three siblings with adrenal hypoplasia congenita.
abstract: Adrenal hypoplasia congenita (AHC) is a rare disease that can be caused by many abnormalities, including an X-linked form. Mutations in the DAX1 gene have been assigned as the genetic cause of AHC. We describe here three siblings with AHC, clinically presented at different ages, two in the neonatal period and one oligosymptomatic during infancy. Molecular analysis was able to detect a novel mutation in exon 1 of the DAX1 gene, consisting of a transition of C to T at position 359, determining a stop codon at position 359 (Q359X). The mutated gene encodes a truncated protein missing a large portion of the ligand-binding domain (C-terminal domain). The recognition of the disease in the index case suggested the diagnosis in the other siblings. Interestingly, the same mutation is presented with different phenotypes, suggesting that first-degree family members of patients with DAX1 mutations should be carefully evaluated routinely.
authors.affiliation: Unidade de Endocrinologia Pediátrica, Departamento de Ciências Fisiológicas, Faculdade de Ciências Médicas, Santa Casa de São Paulo, São Paulo, SP, Brasil. caliari@uol.com.br
authors.forename: L E P
authors.initials: LE
authors.lastname: Calliari
authors.forename: C A
authors.initials: CA
authors.lastname: Longui
authors.forename: M N
authors.initials: MN
authors.lastname: Rocha
authors.forename: C D C
authors.initials: CD
authors.lastname: Faria
authors.forename: C
authors.initials: C
authors.lastname: Kochi
authors.forename: M R
authors.initials: MR
authors.lastname: Melo
authors.forename: M B
authors.initials: MB
authors.lastname: Melo
authors.forename: O
authors.initials: O
authors.lastname: Monte
mesh_terms: D000309:Adrenal Insufficiency / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D035781:Siblings
chemical_list: D018389:Codon, Nonsense; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins