PMID- 19773403
OWN - NLM
STAT- MEDLINE
DCOM- 20091020
LR  - 20161125
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 94
IP  - 10
DP  - 2009 Oct
TI  - Duplications of the functional CYP21A2 gene are primarily restricted to Q318X 
      alleles: evidence for a founder effect.
PG  - 3954-8
LID - 10.1210/jc.2009-0487 [doi]
AB  - CONTEXT: Rare haplotypes with Q318X mutations and duplicated CYP21A2 genes have 
      been reported to occur in different populations to a varying extent. 
      Discrimination between a normal (Q318X mutation on one of the duplicated CYP21A2 
      genes) and a congenital adrenal hyperplasia (CAH, Q318X mutation without 
      duplicated functional gene) allele is of importance, particularly for prenatal 
      diagnosis and the respective genetic counseling. Although methods to 
      differentiate between such alleles have been published only recently, it remains 
      unclear with which frequency Q318X mutations are associated with duplicated 
      CYP21A2 genes and whether these haplotypes have a common ancestry. SUBJECTS AND 
      METHODS: Human leukocyte antigen (HLA) typing has been performed in 38 unrelated 
      individuals and in 11 family members detected to carry a Q318X mutation in the 
      course of CYP21 genotyping using sequence, multiplex ligation-dependent probe 
      amplification, and Southern blot analyses. RESULTS: The majority (n = 32, 84.2%) 
      of the 38 unrelated individuals carrying the Q318X mutation had the trimodular 
      RCCX haplotype, carrying the Q318X mutation on a duplicated CYP21A2 gene. 
      Twenty-two individuals of these 32 (68.8%) were of the rare HLA-B*50-Cw*06 
      haplotype, suggesting a common ancestry of this haplotype. In five (13.2%) of the 
      38 subjects, the Q318X mutation was not associated with a duplicated CYP21A2 gene 
      and thus represents a CAH allele. None of these five patients had the above 
      mentioned HLA haplotype. CONCLUSION: The majority of individuals in whom Q318X 
      mutations are detected carry a duplicated functional CYP21A2 gene and the rare 
      HLA-B*50-Cw*06 haplotype.
FAU - Kleinle, S
AU  - Kleinle S
AD  - Department of Internal Medicine III, Division of Clinical Endocrinology and 
      Metabolism, Medical University of Vienna, A-1090 Vienna, Austria.
FAU - Lang, R
AU  - Lang R
FAU - Fischer, G F
AU  - Fischer GF
FAU - Vierhapper, H
AU  - Vierhapper H
FAU - Waldhauser, F
AU  - Waldhauser F
FAU - Fodinger, M
AU  - Fodinger M
FAU - Baumgartner-Parzer, S M
AU  - Baumgartner-Parzer SM
LA  - eng
PT  - Journal Article
DEP - 20090922
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (HLA-B Antigens)
RN  - 0RH81L854J (Glutamine)
RN  - EC 1.14.14.16 (CYP21A2 protein, human)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
SB  - IM
MH  - Adrenal Hyperplasia, Congenital/diagnosis/genetics
MH  - Adult
MH  - Alleles
MH  - Blotting, Southern
MH  - Female
MH  - *Founder Effect
MH  - Gene Amplification
MH  - *Gene Duplication
MH  - Genotype
MH  - Glutamine
MH  - HLA-B Antigens/*genetics
MH  - Haplotypes
MH  - *Heterozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Steroid 21-Hydroxylase/*genetics
EDAT- 2009/09/24 06:00
MHDA- 2009/10/21 06:00
CRDT- 2009/09/24 06:00
PHST- 2009/09/24 06:00 [entrez]
PHST- 2009/09/24 06:00 [pubmed]
PHST- 2009/10/21 06:00 [medline]
AID - jc.2009-0487 [pii]
AID - 10.1210/jc.2009-0487 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2009 Oct;94(10):3954-8. doi: 10.1210/jc.2009-0487. Epub 
      2009 Sep 22.