Original Article
Analysis of CYP21A2 gene mutations among patients with classical steroid 21-hydroxylase deficiency
Yueqing Su, Hanqiang Chen, Wenbin Zhu, Jing Wang, Jinfu Zhou, Yao Chen, Hong Zhao, Yinglin Zeng, Feng Lin, Honghua Zhang, Qingying Lin
Published 2016-12-10
Cite as Chin J Med Genet, 2016, 33(6): 786-791. DOI: 10.3760/cma.j.issn.1003-9406.2016.06.009
Abstract
ObjectiveTo assess the frequencies of CYP21A2 gene mutations among patients from Fujian area with classical 21-hydroxylase deficiency.
MethodsFor 19 probands from different families affected with classical steroid 21-hydroxylase deficiency and 74 family members, mutations of the CYP21A2 gene were analyzed with combined nested polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification. Time resolved fluorescence immunoassay was performed to determine the level of 17-hydroxyprogesterone (17-OHP) in all family members. Clinical data and laboratory results of the probands and their family members were analyzed.
ResultsEleven mutations were identified among the 38 alleles from the 19 probands. 92.1% (35/38) of the mutant CYP21A2 alleles were due to recombination between CYP21A2 and CYP21A1P. Gene conversion and deletions were identified in 84.2% (32/38) and 7.9% (3/38) of the alleles, respectively. IVS2-13A/C>G and chimeras were the most common mutations, which respectively accounted for 34.2% (13/38) and 18.4% (7/38) of all mutant alleles. Among these, IVS2+ 1G>A and Q318X+ 356W were first reported in China. 74.3% (55/74) of the family members were carriers of heterozygous mutations. However, no significant difference was found in the 17-OHP levels between carriers and non-carriers (P>0.05).
ConclusionThere seems to be a specific spectrum of CYP21A2 gene mutations in Fujian area, where IVS2-13A/C>G and chimeras are the most common mutations.
Key words:
Classical steroid 21-hydroxylase deficiency; Gene mutation; Nested polymerase chain reaction; Gene sequencing; Multiplex ligation-dependent probe amplification
Contributor Information
Yueqing Su
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Hanqiang Chen
Department of Neonatology, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Wenbin Zhu
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Jing Wang
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Jinfu Zhou
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Yao Chen
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Hong Zhao
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Yinglin Zeng
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Feng Lin
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Honghua Zhang
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
Qingying Lin
Center of Neonatal Screening, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China
