title: Late onset X-linked adrenal hypoplasia congenita with hypogonadotropic hypgonadism due to a novel 4-bp deletion in exon 2 of NR0B1.
abstract: We report a novel NR0B1 mutation in a patient affected with X-linked adrenal hypoplasia congenita (X-AHC). The proband first presented with a generalized convulsion at 11 years, 4 months. His clinical and biochemical presentations were consistent with adrenal insufficiency. His basal 17-hydroxyprogesterone (17-OHP) level was not high, and the poor response in 17-OHP on ACTH stimulation test excluded congenital adrenal hyperplasia. At 14 years of age, he did not show any signs of puberty, with low levels of LH, FSH, and testosterone and unresponsiveness to lutenizing hormone releasing hormone stimulation test. Direct DNA sequencing revealed that the proband is hemizygous for a novel NR0B1 mutation (c.1177_1180delGGCC, p.Gly393Cysfs*4). The mother is the conductor of the mutation, which is likely pathogenic as the C-terminus truncated protein lacks the activation function-2 (AF2-TA) transactivation domain, which is highly conserved among members of the nuclear receptor superfamily.
authors.forename: Johari Mohd
authors.initials: JM
authors.lastname: Ali
authors.forename: Muhammad Yazid
authors.identifier: http://orcid.org/0000-0003-4513-8444
authors.initials: MY
authors.lastname: Jalaludin
authors.forename: Fatimah
authors.initials: F
authors.lastname: Harun
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D000309:Adrenal Insufficiency / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D017668:Age of Onset; D002648:Child; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D000075262:Hypoadrenocorticism, Familial; D007006:Hypogonadism / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D017384:Sequence Deletion
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human; D019326:17-alpha-Hydroxyprogesterone