• PMID: 19893922
• Gene Name: DAX1
• Condition: Adrenal hypoplasia congenita
• Association: 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 p
• PMID: 19893922
• Gene Name: DAX1
• Condition: Adrenal hypoplasia congenita
• Association: 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 p
• Mutation: DAX1 (insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution)
• Population size: 2
• Population details: 2 with adrenal hypoplasia congenita
• Sex: Male, female
• Infertility type: Male infertiltiy, Female infertility
• Associated genes: DAX1/NR0B1A
• Other associated phenotypes: Adrenal hypoplasia congenita

Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita

Mantovani RM, Pezzuti IL, Dias VM, Silva IN.

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. CASE REPORT: 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. CONCLUSION: 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. FAU - Mantovani, Rafael Machado AU - Mantovani RM AD - Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil. FAU - Pezzuti, Isabela Leite AU - Pezzuti IL FAU - Dias, Vera Maria Alves AU - Dias VM