Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Chao, Jia, Wenyu, Cheng, Xiangdeng, Ying, Hui, Chen, Jing, Xu, Jin, Guan, Qingbo, Zhou, Xinli, Zheng, Dongmei, Li, Guimei, Zhao, Jiajun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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
_version_ 1783426676950040576
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
work_keys_str_mv AT xuchao genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT jiawenyu genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT chengxiangdeng genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT yinghui genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT chenjing genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT xujin genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT guanqingbo genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT zhouxinli genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT zhengdongmei genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT liguimei genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency
AT zhaojiajun genotypephenotypecorrelationstudyandmutationalandhormonalanalysisinachinesecohortwith21hydroxylasedeficiency