PMID- 10341858
OWN - NLM
STAT- MEDLINE
DCOM- 19990609
LR  - 20190813
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 50
IP  - 1
DP  - 1999 Jan
TI  - Novel DAX1 mutations in X-linked adrenal hypoplasia congenita and
      hypogonadotrophic hypogonadism.
PG  - 69-75
AB  - OBJECTIVE: Mutations of the DAX1 gene (Dosage-sensitive sex reversal-Adrenal
      hypoplasia congenita critical region on the X chromosome gene 1), which encodes a
      novel orphan nuclear receptor, have been identified in patients with X-linked
      adrenal hypoplasia congenita (AHC) and hypogonadotrophic hypogonadism (HHG). We
      have investigated two kindreds with AHC and HHG for DAX1 mutations. METHODS: Two 
      kindreds with five affected males, four carrier females and four unaffected males
      were investigated. The gonadotrophin deficiency in three of the boys was observed
      to be partial until mid-puberty. DAX1 mutations in the entire 1413 bp coding
      region were sought by DNA sequence analysis. RESULTS: Two DAX1 mutations,
      situated within exon 1, were detected. These consisted of an insertional mutation
      at codon 183 that led to a frameshift and a premature Stop at codon 184, and a
      missense mutation Leu278Pro that involved a highly conserved leucine residue
      within the proposed ligand binding domain. Co-segregation of these mutations with
      the disease in each family, and their absence from 107 alleles in 73 (39 males
      and 34 females) unrelated control individuals, was demonstrated by allele
      specific oligonucleotide hybridization (ASO) analysis for the insertional
      mutation, and by Ban I restriction endonuclease analysis for the missense
      mutation. CONCLUSIONS: Two novel DAX1 mutations have been detected in two
      families with adrenal hypoplasia and hypogonadotrophic hypogonadism. The finding 
      of partial gonadotrophin deficiency in the affected males from these families is 
      notable and an early recognition of such a possibility in a patient, which may be
      facilitated by DAX1 mutational analysis, may help to prevent the sequelae of
      delayed androgen replacement therapy.
FAU - Bassett, J H
AU  - Bassett JH
AD  - MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith
      Hospital, London, UK.
FAU - O'Halloran, D J
AU  - O'Halloran DJ
FAU - Williams, G R
AU  - Williams GR
FAU - Beardwell, C G
AU  - Beardwell CG
FAU - Shalet, S M
AU  - Shalet SM
FAU - Thakker, R V
AU  - Thakker RV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (DAX-1 Orphan Nuclear Receptor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NR0B1 protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
SB  - IM
MH  - Adolescent
MH  - Adrenal Insufficiency/blood/*congenital/*genetics
MH  - Child
MH  - Child, Preschool
MH  - DAX-1 Orphan Nuclear Receptor
MH  - DNA Mutational Analysis
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - Follicle Stimulating Hormone/blood
MH  - Frameshift Mutation
MH  - Gonadotropin-Releasing Hormone
MH  - Humans
MH  - Hypogonadism/blood/*congenital/*genetics
MH  - Infant
MH  - Infant, Newborn
MH  - Luteinizing Hormone/blood
MH  - Male
MH  - *Mutation
MH  - Mutation, Missense
MH  - Receptors, Retinoic Acid/*genetics
MH  - *Repressor Proteins
MH  - Sequence Analysis, DNA
MH  - Transcription Factors/*genetics
MH  - *X Chromosome
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
AID - 10.1046/j.1365-2265.1999.00601.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 1999 Jan;50(1):69-75. doi:
      10.1046/j.1365-2265.1999.00601.x.