Novel non-stop variant of the NR0B1 gene in two siblings with adrenal hypoplasia congenita

Abstract

Objectives Mutations in the dosage-sensitive sex reversal-AHC critical region on the X chromosome, gene 1 (DAX-1, officially NR0B1), cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). Salt-losing adrenal insufficiency usually occurs during the neonatal period or early childhood. We report a novel non-stop variant of NR0B1 in two siblings and their unusual clinical course. Case presentation The proband was a boy who presented with an unusual form of AHC with neonatal onset of growth failure and mild salt loss, but without cutaneous pigmentation or plasma ACTH elevation. His 4-year-old elder brother had been growing healthily, but carried an AHC diagnosis. A non-stop variant of NR0B1 (p.*471K) was demonstrated in the patients and their mother. Conclusions We identified a novel non-stop variant of NR0B1 in two siblings. Mild salt loss associated with hyperkalemia is a crucial diagnostic clue for AHC, even without apparent symptoms of glucocorticoid deficiency.

Addison’s Disease: Diagnosis and Management Strategies

“… 55 Another novel mutation of NR0B1 ( DAX-1 ) gene (p.*471K) was reported in two siblings with different clinical manifestations who inherited the mutation from their mother. 56 A novel frameshift mutation was described in adult X-linked onset congenital adrenal hypoplasia with delayed puberty in a male harboring NR0B1 gene : c.1034delC (exon 1). 57 Of note, a carrier of NROB1 variant experienced transitory central precocious puberty by the age of 11 months that remitted after hydrocortisone replacement for AD.…”