high frequency of copy number variations and sequence variants at cyp21a2 locus implication for the genetic diagnosis of 21-hydroxylase deficiency高拷贝数变化的频率和序列变异cyp21a2轨迹隐含21-hydroxylase基因诊断的不足之处.pdfVIP

High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency 1 1 ´ 1,2 1 Silvia Parajes , Celsa Quinteiro , Fernando Domınguez , Lourdes Loidi * ´ ´ ´ ´ ˜ 1 Fundacion Publica Galega de Medicina Xenomica (Unidad de Medicina Molecular), Hospital Clınico Universitario, Santiago de Compostela, A Coruna, Spain, ´ ˜ 2 Departamento de Fisiologıa, Universidad de Santiago de Compostela, Santiago de Compostela, A Coruna, Spain Abstract Background: The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1:25 to 1:10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling Methodology and Findings: CYP21A2 genoty