PMID- 7677150
OWN - NLM
STAT- MEDLINE
DCOM- 19951019
LR  - 20161123
IS  - 0148-7299 (Print)
IS  - 0148-7299 (Linking)
VI  - 57
IP  - 3
DP  - 1995 Jul 3
TI  - Splicing mutation in CYP21 associated with delayed presentation of salt-wasting 
      congenital adrenal hyperplasia.
PG  - 450-4
AB  - Patients with salt-wasting congenital adrenal hyperplasia (SW-CAH) most commonly 
      carry an A-G transition at nucleotide 656 (nt 656 A-->G), causing abnormal 
      splicing of exons 2 and 3 in CYP21, the gene encoding active steroid 
      21-hydroxylase. Affected infants are severely deficient in cortisol and 
      aldosterone, and usually come to medical attention during the neonatal period. We 
      report on 2 affected boys, homozygous for the nt 656 mutation, who thrived in 
      early infancy, but suffered salt-wasting crises unusually late in infancy, at 3.5 
      and 5.5 months, respectively. Laboratory studies at presentation showed 
      hyponatremia, hyperkalemia, dehydration, and acidosis; serum aldosterone was low 
      in spite of markedly elevated plasma renin activity. Basal 17-hydroxyprogesterone 
      levels were only moderately elevated, yet the stimulated levels were more typical 
      of severe, classic CAH due to 21-hydroxylase deficiency. Genomic DNA from the 
      patients was analyzed. Southern blot showed no major deletions or rearrangements. 
      CYP21-specific amplification by polymerase chain reaction, coupled with 
      allele-specific hybridization using wild-type and mutant probes at each of 9 
      sites for recognized disease-causing mutations, revealed a single, homozygous 
      mutation in each patient: nt 656 A-->G. These results were confirmed by sequence 
      analysis. We conclude that the common nt 656 A-->G mutation is sometimes 
      associated with delayed phenotypic expression of SW-CAH. We speculate that 
      variable splicing of the mutant CYP21 may modify the clinical manifestations of 
      this disease.
FAU - Kohn, B
AU  - Kohn B
AD  - Department of Pediatrics, Long Island College, Brooklyn, New York, USA.
FAU - Day, D
AU  - Day D
FAU - Alemzadeh, R
AU  - Alemzadeh R
FAU - Enerio, D
AU  - Enerio D
FAU - Patel, S V
AU  - Patel SV
FAU - Pelczar, J V
AU  - Pelczar JV
FAU - Speiser, P W
AU  - Speiser PW
LA  - eng
GR  - HD-00072/HD/NICHD NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Med Genet
JT  - American journal of medical genetics
JID - 7708900
RN  - 0 (DNA Primers)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
SB  - IM
GS  - CYP21
MH  - Acidosis/complications/genetics
MH  - Adrenal Hyperplasia, Congenital/blood/complications/*genetics
MH  - Base Sequence
MH  - DNA Primers
MH  - Dehydration/complications/genetics
MH  - Homozygote
MH  - Humans
MH  - Hyperkalemia/complications/genetics
MH  - Hyponatremia/complications/*genetics
MH  - Infant
MH  - Male
MH  - Molecular Sequence Data
MH  - *Point Mutation
MH  - Polymerase Chain Reaction
MH  - *RNA Splicing
MH  - Steroid 21-Hydroxylase/*genetics
EDAT- 1995/07/03 00:00
MHDA- 1995/07/03 00:01
CRDT- 1995/07/03 00:00
PHST- 1995/07/03 00:00 [pubmed]
PHST- 1995/07/03 00:01 [medline]
PHST- 1995/07/03 00:00 [entrez]
AID - 10.1002/ajmg.1320570318 [doi]
PST - ppublish
SO  - Am J Med Genet. 1995 Jul 3;57(3):450-4. doi: 10.1002/ajmg.1320570318.