Arquivos Brasileiros de Endocrinologia & Metabologia
On-line version ISSN 1677-9487
MANTOVANI, Rafael Machado; PEZZUTI, Isabela Leite; DIAS, Vera Maria Alves and SILVA, Ivani Novato. Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita. Arq Bras Endocrinol Metab [online]. 2009, vol.53, n.6, pp.771-776. ISSN 1677-9487. http://dx.doi.org/10.1590/S0004-27302009000600013.
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.
Keywords : Congenital [hereditary]; Congenital [neonatal diseases]; Congenital [abnormalities]; adrenal insufficiency; frameshift mutation; genetic counseling.