X-linked adrenal hypoplasia congenita: clinical and follow-up findings of two kindreds, one with a novel NR0B1 mutation
Arch. endocrinol. metab. (Online)
;
59(2): 181-185, 04/2015. tab, graf
Article
Dans Anglais
| LILACS
| ID: lil-746466
ABSTRACT
X-linked adrenal hypoplasia congenita typically manifests as primary adrenal insufficiency in the newborn age and hypogonadotropic hypogonadism in males, being caused by mutations in NR0B1 gene. We present the clinical and follow-up findings of two kindreds with NR0B1 mutations. The proband of kindred A had a diagnosis of primary adrenal insufficiency when he was a newborn. Family history was relevant for a maternal uncle death at the newborn age. Beyond 2 year-old steroid measurements rendered undetectable and delayed bone age was noticed. Molecular analysis of NR0B1 gene revealed a previously unreported mutation (c.1084A>T), leading to a premature stop codon, p.Lys362*, in exon 1. His mother and sister were asymptomatic carriers. At 14 year-old he had 3 mL of testicular volume and biochemical surveys (LH < 0.1 UI/L, total testosterone < 10 ng/dL) concordant with hypogonadotrophic hypogonadism. Kindred B had two males diagnosed with adrenal insufficiency at the newborn age. By 3 year-old both siblings had undetectable androgen levels and delayed bone age. NR0B1 molecular analysis identified a nonsense mutation in both cases, c.243C>G; p.Tyr81*, in exon 1. Their mother and sister were asymptomatic carriers. At 14 year-old (Tanner stage 1) hypothalamic-pituitary-gonadal axis evaluation in both males (LH < 0.1UI/L, total testosterone < 10 ng/dL) confirmed hypogonadotropic hypogonadism. In conclusion, biochemical profiles, bone age and an X-linked inheritance led to suspicion of NR0B1 mutations. Two nonsense mutations were detected in both kindreds, one previously unreported (c.1084A>T; p.Lys362*). Mutation identification allowed the timely institution of testosterone in patients at puberty and an appropriate genetic counselling for relatives.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Insuffisance surrénale
/
Maladies génétiques liées au chromosome X
/
Récepteur nucléaire orphelin DAX-1
/
Mutation
Type d'étude:
Etude diagnostique
/
Étude observationnelle
/
Étude pronostique
Limites du sujet:
Humains
/
Bébé
/
Mâle
/
Nouveau-né
langue:
Anglais
Texte intégral:
Arch. endocrinol. metab. (Online)
Thème du journal:
Endocrinologie
/
Métabolisme
Année:
2015
Type:
Article
Pays d'affiliation:
Portugal
Institution/Pays d'affiliation:
Hospital Garcia de Orta – E.P.E/PT
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS