title: Analysis of the CYP21A1P pseudogene: indication of mutational diversity and CYP21A2-like and duplicated CYP21A2 genes.
abstract: The CYP21A1P gene downstream of the XA gene, carrying 15 deteriorated mutations, is a nonfunctional pseudogene that shares 98% nucleotide sequence homology with CYP21A2 located on chromosome 6p21.3. However, these mutations in the CYP21A1P gene are not totally involved in each individual. From our analysis of 100 healthy ethnic Chinese (i.e., Taiwanese) (n=200 chromosomes) using the polymerase chain reaction (PCR) products combined with an amplification-created restriction site (ACRS) method and DNA sequencing, we found that approximately 10% of CYP21A1P alleles (n=195 chromosomes) presented the CYP21A2 sequence; frequencies of P30, V281, Q318, and R356 in that locus were approximately 24%, 21%, 11%, and 34%, respectively, and approximately 90% of the CYP21A1P alleles had 15 mutated loci. In addition, approximately 2.5% (n=5 chromosomes) showed four haplotypes of the 3.7-kb TaqI-produced fragment of the CYP21A2-like gene and one duplicated CYP21A2 gene. We conclude that the pseudogene of the CYP21A1P mutation presents diverse variants. Moreover, the existence of the CYP21A2-like gene is more abundant than that of the duplicated CYP21A2 gene downstream of the XA gene and could not be distinguished from the CYP21A2-TNXB gene; thus, it may be misdiagnosed by previously established methods for congenital adrenal hyperplasia caused by a 21-hydroxylase deficiency.
authors.affiliation: Department of Pediatrics, Buddhist Tzu Chi General Hospital, Taipei Branch, Sindian, Taipei County 231, Taiwan.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Tsai
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Chuang
authors.forename: Hsien-Hsiung
authors.initials: HH
authors.lastname: Lee
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics; D044466:Asian People; D001483:Base Sequence; D005787:Gene Frequency; D020131:Genes, Duplicate; D056726:Genetic Association Studies; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006801:Humans; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011544:Pseudogenes; D015183:Restriction Mapping / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D019063:Tenascin / Q000235:genetics
chemical_list: D019063:Tenascin; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase