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21-hydroxylase deficiency-induced congenital adrenal hyperplasia in 230 Chinese patients: Genotype-phenotype correlation and identification of nine novel mutations.
Steroids. 2016 Apr; 108:47-55.S

Abstract

Steroid 21-hydroxylase deficiency (21-OHD) caused by the CYP21A2 gene mutations accounts for more than 90% of congenital adrenal hyperplasia (CAH) cases. In this study, molecular defects of 230 patients with 21-OHD were investigated. Point mutations of CYP21A2 gene were analyzed by Sanger sequencing, and large gene deletions were detected by multiplex ligation-dependent probe amplification (MLPA). Nine micro-conversions and 18 spontaneous mutations accounted for 74.6% of alleles, while large gene deletions and large gene conversions accounted for 25.4% of alleles. The most frequent micro-conversion was c.292-13A/C>G (I2G) (35%), followed by p.I173N (14.3%), p.R357W (5.9%) and p.Q319* (4.6%). Nine novel mutations were identified in these patients, which were predicted to hamper the 21-hydroxylase protein function in varying degrees. Genotype and phenotype correlated well in 89.6% of our patients, but disparity in phenotypic appearance also appeared in a small portion of the patients. 16.1% of the patients carried homozygous genotypes while 83.9% of patients carried compound heterozygous mutations. We concluded that the frequency of CYP21A2 mutations in our study was slightly different from those reported for other ethnic groups. Micro-conversions were the main category of the mutation spectrum, while large deletions and large gene conversions could also cause 21-OHD. A large portion of different types of the compound heterozygous genotypes may partially contribute to the discordance in genotype-phenotype comparison. This study expanded the CYP21A2 mutation spectrum of Chinese patients and could be helpful in prenatal diagnosis and genetic counseling for 21-OHD patients.

Authors+Show Affiliations

Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China. Electronic address: gu_xuefan@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26804566

Citation

Wang, Ruifang, et al. "21-hydroxylase Deficiency-induced Congenital Adrenal Hyperplasia in 230 Chinese Patients: Genotype-phenotype Correlation and Identification of Nine Novel Mutations." Steroids, vol. 108, 2016, pp. 47-55.
Wang R, Yu Y, Ye J, et al. 21-hydroxylase deficiency-induced congenital adrenal hyperplasia in 230 Chinese patients: Genotype-phenotype correlation and identification of nine novel mutations. Steroids. 2016;108:47-55.
Wang, R., Yu, Y., Ye, J., Han, L., Qiu, W., Zhang, H., Liang, L., Gong, Z., Wang, L., & Gu, X. (2016). 21-hydroxylase deficiency-induced congenital adrenal hyperplasia in 230 Chinese patients: Genotype-phenotype correlation and identification of nine novel mutations. Steroids, 108, 47-55. https://doi.org/10.1016/j.steroids.2016.01.007
Wang R, et al. 21-hydroxylase Deficiency-induced Congenital Adrenal Hyperplasia in 230 Chinese Patients: Genotype-phenotype Correlation and Identification of Nine Novel Mutations. Steroids. 2016;108:47-55. PubMed PMID: 26804566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 21-hydroxylase deficiency-induced congenital adrenal hyperplasia in 230 Chinese patients: Genotype-phenotype correlation and identification of nine novel mutations. AU - Wang,Ruifang, AU - Yu,Yongguo, AU - Ye,Jun, AU - Han,Lianshu, AU - Qiu,Wenjuan, AU - Zhang,Huiwen, AU - Liang,Lili, AU - Gong,Zhuwen, AU - Wang,Lili, AU - Gu,Xuefan, Y1 - 2016/01/21/ PY - 2015/08/24/received PY - 2016/01/12/revised PY - 2016/01/14/accepted PY - 2016/1/26/entrez PY - 2016/1/26/pubmed PY - 2016/12/15/medline KW - 21-Hydroxylase deficiency KW - CYP21A2 gene KW - Congenital adrenal hyperplasia KW - Genotype–phenotype correlation KW - Mutational spectrum SP - 47 EP - 55 JF - Steroids JO - Steroids VL - 108 N2 - Steroid 21-hydroxylase deficiency (21-OHD) caused by the CYP21A2 gene mutations accounts for more than 90% of congenital adrenal hyperplasia (CAH) cases. In this study, molecular defects of 230 patients with 21-OHD were investigated. Point mutations of CYP21A2 gene were analyzed by Sanger sequencing, and large gene deletions were detected by multiplex ligation-dependent probe amplification (MLPA). Nine micro-conversions and 18 spontaneous mutations accounted for 74.6% of alleles, while large gene deletions and large gene conversions accounted for 25.4% of alleles. The most frequent micro-conversion was c.292-13A/C>G (I2G) (35%), followed by p.I173N (14.3%), p.R357W (5.9%) and p.Q319* (4.6%). Nine novel mutations were identified in these patients, which were predicted to hamper the 21-hydroxylase protein function in varying degrees. Genotype and phenotype correlated well in 89.6% of our patients, but disparity in phenotypic appearance also appeared in a small portion of the patients. 16.1% of the patients carried homozygous genotypes while 83.9% of patients carried compound heterozygous mutations. We concluded that the frequency of CYP21A2 mutations in our study was slightly different from those reported for other ethnic groups. Micro-conversions were the main category of the mutation spectrum, while large deletions and large gene conversions could also cause 21-OHD. A large portion of different types of the compound heterozygous genotypes may partially contribute to the discordance in genotype-phenotype comparison. This study expanded the CYP21A2 mutation spectrum of Chinese patients and could be helpful in prenatal diagnosis and genetic counseling for 21-OHD patients. SN - 1878-5867 UR - https://www.unboundmedicine.com/medline/citation/26804566/21_hydroxylase_deficiency_induced_congenital_adrenal_hyperplasia_in_230_Chinese_patients:_Genotype_phenotype_correlation_and_identification_of_nine_novel_mutations_ DB - PRIME DP - Unbound Medicine ER -