title: Rare mutations in the CYP21A2 gene detected in congenital adrenal hyperplasia.
abstract: OBJECTIVE
  The purpose of this study was to identify and determine the frequencies of rare CYP21A2 gene mutations in patients with 21-hydroxylase deficiency (21-OHD) in the Cypriot population.
  
  
  METHODS
  Direct sequencing and MLPA analysis of the CYP21A2 gene.
  
  
  RESULTS
  A group of families with 21-OHD were screened for the presence of rare CYP21A2 gene mutations. The rare V304M missense mutation was detected as compound heterozygous in two females with the nonclassical (NC) form of congenital adrenal hyperplasia (CAH). The rare F306insT was also detected in a female with severe salt wasting in the homozygous state and in cis in both alleles with the V281L mutation. Lastly, the rare A391T missense mutation was reported in a female patient with NC-CAH. A carrier rate of 2.1% for the V304M was also observed in a cohort of healthy controls.
  
  
  CONCLUSIONS
  The frequency of V304M mutation among Cypriots is high and the first reported so far and patients characterized as compound heterozygotes or heterozygotes are most readily identified by a mild phenotype of CAH. Thus, V304M should be included in the panel of mutations associated with the NC forms of 21-OHD.
authors.affiliation: Department of Molecular Genetics Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
authors.forename: Vassos
authors.initials: V
authors.lastname: Neocleous
authors.forename: Yiannis S
authors.initials: YS
authors.lastname: Ioannou
authors.forename: Margarita
authors.initials: M
authors.lastname: Bartsota
authors.forename: Constandina
authors.initials: C
authors.lastname: Costi
authors.forename: Nicos
authors.initials: N
authors.lastname: Skordis
authors.forename: Leonidas A
authors.initials: LA
authors.lastname: Phylactou
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D002648:Child; D003535:Cyprus; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D020125:Mutation, Missense; D013255:Steroid 21-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase; C048422:endodeoxyribonuclease NlaIII; D015252:Deoxyribonucleases, Type II Site-Specific