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Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency
BACKGROUND: Steroid 21‐hydroxylase deficiency (21OHD) is the most common enzymatic defect, but the genotype–phenotype associations have not been well established in Chinese patients. Here, a Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of th...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565591/ https://www.ncbi.nlm.nih.gov/pubmed/30968594 http://dx.doi.org/10.1002/mgg3.671 |
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author | Xu, Chao Jia, Wenyu Cheng, Xiangdeng Ying, Hui Chen, Jing Xu, Jin Guan, Qingbo Zhou, Xinli Zheng, Dongmei Li, Guimei Zhao, Jiajun |
author_facet | Xu, Chao Jia, Wenyu Cheng, Xiangdeng Ying, Hui Chen, Jing Xu, Jin Guan, Qingbo Zhou, Xinli Zheng, Dongmei Li, Guimei Zhao, Jiajun |
author_sort | Xu, Chao |
collection | PubMed |
description | BACKGROUND: Steroid 21‐hydroxylase deficiency (21OHD) is the most common enzymatic defect, but the genotype–phenotype associations have not been well established in Chinese patients. Here, a Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder. METHODS: Mutation analysis of CYP21A2 gene, 21‐hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype–phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported. RESULTS: Among the total cohort (72 patients), 47 patients (65.3%) were diagnosed as salt‐wasting (SW) phenotype, 11 (15.3%) were simple virilizing (SV) type, and 14 (19.4%) were nonclassic (NC) type. The value of FSH and LH for prediction of the SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q, and p.L459‐P464del) were detected and induced a significantly reduced 21‐hydroxylase activity. Generally, disease severity can be predicted with the genotypes. The most common genotypes in Chinese population were I2G/I2G (12.5%), I2G/Large lesion (12.1%), I173N/I2G (10.3%), and I173N/Large lesion (9.2%). The SW form of CAH is prominent in deletion or intronic splice mutations, namely I2G/I2G (18.6%), I2G/Large lesion (17.2%) and Large lesion/Large lesion (8.6%). CONCLUSION: Four novel mutations were identified and a high consistency of genotype–phenotype association was found in SW CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease. |
format | Online Article Text |
id | pubmed-6565591 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65655912019-06-20 Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency Xu, Chao Jia, Wenyu Cheng, Xiangdeng Ying, Hui Chen, Jing Xu, Jin Guan, Qingbo Zhou, Xinli Zheng, Dongmei Li, Guimei Zhao, Jiajun Mol Genet Genomic Med Original Articles BACKGROUND: Steroid 21‐hydroxylase deficiency (21OHD) is the most common enzymatic defect, but the genotype–phenotype associations have not been well established in Chinese patients. Here, a Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder. METHODS: Mutation analysis of CYP21A2 gene, 21‐hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype–phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported. RESULTS: Among the total cohort (72 patients), 47 patients (65.3%) were diagnosed as salt‐wasting (SW) phenotype, 11 (15.3%) were simple virilizing (SV) type, and 14 (19.4%) were nonclassic (NC) type. The value of FSH and LH for prediction of the SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q, and p.L459‐P464del) were detected and induced a significantly reduced 21‐hydroxylase activity. Generally, disease severity can be predicted with the genotypes. The most common genotypes in Chinese population were I2G/I2G (12.5%), I2G/Large lesion (12.1%), I173N/I2G (10.3%), and I173N/Large lesion (9.2%). The SW form of CAH is prominent in deletion or intronic splice mutations, namely I2G/I2G (18.6%), I2G/Large lesion (17.2%) and Large lesion/Large lesion (8.6%). CONCLUSION: Four novel mutations were identified and a high consistency of genotype–phenotype association was found in SW CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease. John Wiley and Sons Inc. 2019-04-09 /pmc/articles/PMC6565591/ /pubmed/30968594 http://dx.doi.org/10.1002/mgg3.671 Text en © 2019 The Shandong Provincial Hospital. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Xu, Chao Jia, Wenyu Cheng, Xiangdeng Ying, Hui Chen, Jing Xu, Jin Guan, Qingbo Zhou, Xinli Zheng, Dongmei Li, Guimei Zhao, Jiajun Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency |
title | Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency |
title_full | Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency |
title_fullStr | Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency |
title_full_unstemmed | Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency |
title_short | Genotype–phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21‐hydroxylase deficiency |
title_sort | genotype–phenotype correlation study and mutational and hormonal analysis in a chinese cohort with 21‐hydroxylase deficiency |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565591/ https://www.ncbi.nlm.nih.gov/pubmed/30968594 http://dx.doi.org/10.1002/mgg3.671 |
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