PMID- 22014889
OWN - NLM
STAT- MEDLINE
DCOM- 20120718
LR  - 20211025
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 61
IP  - 4
DP  - 2012 Apr
TI  - p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital adrenal 
      hyperplasia patients.
PG  - 519-24
LID - 10.1016/j.metabol.2011.08.008 [doi]
AB  - More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from 
      steroid 21-hydroxylase gene (CYP21A2) mutations. The CYP21A2 gene is located in 
      the human leukocyte antigen (HLA) class III region on the short arm of chromosome 
      6p21.3, along with an inactive pseudogene, CYP21A1P, that is 98% homologous in 
      its coding sequence with CYP21A2. Most CYP21A2 mutations result from intergenic 
      recombinations between CYP21A2 and the closely linked CYP21A1P pseudogene. Rare 
      mutations not generated by gene conversion account for only 5% to 10% of 
      21-hydroxylase deficiency alleles. However, detection of these rare and 
      spontaneous mutations has continued to expand worldwide. We identified 2 novel 
      CYP21A2 missense mutations (p.H282N and p.Y191H) in 2 Italian patients with 
      simple-virilizing and nonclassic CAH forms. Functional analysis of these CYP21A2 
      mutations was performed. Functional in vitro assay for mutagenized CYP21A2 
      enzymes was performed in transiently transfected mammalian cells to test the 
      residual enzyme activity and the apparent kinetic values. The residual activities 
      obtained allowed us to classify the p.H282N and p.Y191H variants as 
      simple-virilizing and nonclassic CAH associated mutations, respectively. These 
      results correlate with the rate of severity of the patients' disease. This 
      finding provides a further contribution for assisting in the diagnosis of CAH 
      patients.
CI  - Copyright A(c) 2012 Elsevier Inc. All rights reserved.
FAU - Concolino, Paola
AU  - Concolino P
AD  - Laboratory of Molecular Biology, Institute of Biochemistry and Clinical 
      Biochemistry, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy. 
      paolaconcolino78@libero.it
FAU - Mello, Enrica
AU  - Mello E
FAU - Patrosso, Maria Cristina
AU  - Patrosso MC
FAU - Penco, Silvana
AU  - Penco S
FAU - Zuppi, Cecilia
AU  - Zuppi C
FAU - Capoluongo, Ettore
AU  - Capoluongo E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111019
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 9007-49-2 (DNA)
RN  - EC 1.14.14.16 (CYP21A2 protein, human)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
RN  - Congenital adrenal hyperplasia due to 21 hydroxylase deficiency
SB  - IM
MH  - Adrenal Hyperplasia, Congenital/*enzymology/genetics
MH  - Adult
MH  - Animals
MH  - Blotting, Western
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - DNA/chemistry/genetics
MH  - Female
MH  - Genetic Variation
MH  - Humans
MH  - Male
MH  - Mutagenesis, Site-Directed/methods
MH  - *Mutation, Missense
MH  - Steroid 21-Hydroxylase/*genetics
MH  - Transfection
EDAT- 2011/10/22 06:00
MHDA- 2012/07/19 06:00
CRDT- 2011/10/22 06:00
PHST- 2011/07/04 00:00 [received]
PHST- 2011/08/19 00:00 [revised]
PHST- 2011/08/19 00:00 [accepted]
PHST- 2011/10/22 06:00 [entrez]
PHST- 2011/10/22 06:00 [pubmed]
PHST- 2012/07/19 06:00 [medline]
AID - S0026-0495(11)00274-5 [pii]
AID - 10.1016/j.metabol.2011.08.008 [doi]
PST - ppublish
SO  - Metabolism. 2012 Apr;61(4):519-24. doi: 10.1016/j.metabol.2011.08.008. Epub 2011 
      Oct 19.