PMID- 10843183
OWN - NLM
STAT- MEDLINE
DCOM- 20000616
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 5
DP  - 2000 May
TI  - A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-wasting 
      3beta-hydroxysteroid dehydrogenase deficiency in 46,XX and 46,XY 
      French-Canadians: evaluation of gonadal function after puberty.
PG  - 1968-74
AB  - Severe 3beta-hydroxysteroid dehydrogenase (3betaHSD) deficiency is a rare form of 
      congenital adrenal hyperplasia resulting from mutations in the HSD3B2 gene that 
      impair steroidogenesis in both the adrenals and gonads and cause salt-wasting in 
      both sexes and incomplete masculinization of the external genitalia in genetic 
      males. About two thirds of the reported patients are 46,XY. We describe two 
      French-Canadian patients from two families without a known relationship who 
      presented with severe salt-wasting 3betaHSD deficiency in infancy. Although the 
      diagnosis was considered clinically, plasma steroid profiles were confusing. We 
      have thus directly sequenced DNA fragments generated by PCR amplification of the 
      four exons, exon-intron boundaries, and the 5'-flanking regions of the HSD3B2 
      gene. Sequencing of exon II revealed the presence of a C to A transversion in 
      both alleles of these two cases, thus converting codon 10 (GCA), which codes for 
      Ala, into GAA, encoding Glu. This Ala is highly conserved in the vertebrate 
      3betaHSD gene family and is located in the putative NAD-binding domain of the 
      enzyme. The mutant type II 3betaHSD enzyme carrying an A10E substitution 
      exhibited no detectable activity in intact transfected Ad293 cells. Both 
      homozygous patients share the same haplotype, spanning approximately 3.3 
      centimorgans surrounding the HSD3B2 locus, which is consistent with a founder 
      effect for this missense mutation. The 46,XY patient presented with ambiguous 
      genitalia at birth and underwent normal masculinization at puberty, but was 
      azoospermic at 18.5 yr of age. The 46,XX patient presented progressive breast 
      development, menarche, and evidence of progesterone secretion. The only 
      previously reported cases with pubertal follow-up revealed paternity in one male 
      and hypogonadism in one female. These findings demonstrate the complex 
      relationships between the genotype and the gonadal phenotype in severe 3betaHSD 
      deficiency and the difficulty in predicting fertility.
FAU - Alos, N
AU  - Alos N
AD  - Departement de Pediatrie, Universite de Montreal, Canada.
FAU - Moisan, A M
AU  - Moisan AM
FAU - Ward, L
AU  - Ward L
FAU - Desrochers, M
AU  - Desrochers M
FAU - Legault, L
AU  - Legault L
FAU - Leboeuf, G
AU  - Leboeuf G
FAU - Van Vliet, G
AU  - Van Vliet G
FAU - Simard, J
AU  - Simard J
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Genetic Markers)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 3-Hydroxysteroid Dehydrogenases/*deficiency/*genetics
MH  - Adolescent
MH  - Adrenal Hyperplasia, Congenital/*genetics/*physiopathology
MH  - Amino Acid Substitution
MH  - Base Sequence
MH  - Canada
MH  - Child
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 1
MH  - Consanguinity
MH  - Female
MH  - Founder Effect
MH  - France/ethnology
MH  - Genetic Markers
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Microsatellite Repeats
MH  - Mutagenesis, Site-Directed
MH  - *Mutation, Missense
MH  - Nuclear Family
MH  - Polymerase Chain Reaction
MH  - Puberty
EDAT- 2000/06/08 09:00
MHDA- 2000/06/24 11:00
CRDT- 2000/06/08 09:00
PHST- 2000/06/08 09:00 [pubmed]
PHST- 2000/06/24 11:00 [medline]
PHST- 2000/06/08 09:00 [entrez]
AID - 10.1210/jcem.85.5.6581 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 May;85(5):1968-74. doi: 10.1210/jcem.85.5.6581.