The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohort
Abstract Background 21‐Hydroxylase deficiency (21‐OHD) caused by the CYP21A2 gene mutations is the most common form of congenital adrenal hyperplasia. It is an autosomal recessive disorder that results in defective synthesis of cortisol and aldosterone. The incidences of various CYP21A2 gene mutatio...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-11-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1501 |
| _version_ | 1797300984121131008 |
|---|---|
| author | Yang Liu Jie Zheng Nan Liu Xiaowei Xu Xinjie Zhang Ying Zhang Guoxu Li Geli Liu Chunquan Cai Jianbo Shu |
| author_facet | Yang Liu Jie Zheng Nan Liu Xiaowei Xu Xinjie Zhang Ying Zhang Guoxu Li Geli Liu Chunquan Cai Jianbo Shu |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | Abstract Background 21‐Hydroxylase deficiency (21‐OHD) caused by the CYP21A2 gene mutations is the most common form of congenital adrenal hyperplasia. It is an autosomal recessive disorder that results in defective synthesis of cortisol and aldosterone. The incidences of various CYP21A2 gene mutations and the genotype–phenotype correlations vary among different populations. Materials and Methods The clinical and molecular data of 22 patients were analyzed in this study. All patients were recruited from the neonatal intensive care unit. Locus‐specific polymerase chain reaction and Sanger sequencing were applied to identify gene micro‐conversions, and multiplex ligation‐dependent probe amplification was used to detect large fragment deletions/conversions. Then, the genotypes were categorized in to Null, A, B, C, and D groups to analyze the relationships between genotypes and phenotypes. Results All 22 patients were classified into classic salt wasting form of 21‐OHD. Molecular defects were detected in 44 alleles (100%). Micro‐conversion mutation IVS2‐13A/C>G (70.5%) is most common in our cohort, followed by large gene deletions and conversions (22.7%). The other mutations present were p.R357 W (4.5%) and E6 Cluster (2.3%). Genotypes of 22 patients (100%) were consistent with the predictive phenotypes. Conclusion In this study, we identified the mutation spectrum of CYP21A2 gene in Chinese patients, especially the younger age cohort in pediatrics. Micro‐conversions were the most popular mutations. Moreover, the genotypes and phenotypes were well correlated in this cohort of salt wasting 21‐OHD recruited from neonatal intensive care unit. |
| first_indexed | 2024-03-07T23:15:48Z |
| format | Article |
| id | doaj.art-378a6828cdfc49fcabe6f843d3a3a57f |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:15:48Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-378a6828cdfc49fcabe6f843d3a3a57f2024-02-21T11:47:09ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-11-01811n/an/a10.1002/mgg3.1501The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohortYang Liu0Jie Zheng1Nan Liu2Xiaowei Xu3Xinjie Zhang4Ying Zhang5Guoxu Li6Geli Liu7Chunquan Cai8Jianbo Shu9Department of Neonatology Tianjin Children’s Hospitalthe Pediatric Clinical College in Tianjin Medical University Tianjin ChinaGraduate College of Tianjin Medical University Tianjin ChinaGraduate College of Tianjin Medical University Tianjin ChinaTianjin Children’s Hospital (Children’s Hospital of Tianjin University Tianjin ChinaTianjin Children’s Hospital (Children’s Hospital of Tianjin University Tianjin ChinaGraduate College of Tianjin Medical University Tianjin ChinaGraduate College of Tianjin Medical University Tianjin ChinaDepartment of Pediatrics Tianjin Medical University General Hospital Tianjin ChinaTianjin Children’s Hospital (Children’s Hospital of Tianjin University Tianjin ChinaTianjin Children’s Hospital (Children’s Hospital of Tianjin University Tianjin ChinaAbstract Background 21‐Hydroxylase deficiency (21‐OHD) caused by the CYP21A2 gene mutations is the most common form of congenital adrenal hyperplasia. It is an autosomal recessive disorder that results in defective synthesis of cortisol and aldosterone. The incidences of various CYP21A2 gene mutations and the genotype–phenotype correlations vary among different populations. Materials and Methods The clinical and molecular data of 22 patients were analyzed in this study. All patients were recruited from the neonatal intensive care unit. Locus‐specific polymerase chain reaction and Sanger sequencing were applied to identify gene micro‐conversions, and multiplex ligation‐dependent probe amplification was used to detect large fragment deletions/conversions. Then, the genotypes were categorized in to Null, A, B, C, and D groups to analyze the relationships between genotypes and phenotypes. Results All 22 patients were classified into classic salt wasting form of 21‐OHD. Molecular defects were detected in 44 alleles (100%). Micro‐conversion mutation IVS2‐13A/C>G (70.5%) is most common in our cohort, followed by large gene deletions and conversions (22.7%). The other mutations present were p.R357 W (4.5%) and E6 Cluster (2.3%). Genotypes of 22 patients (100%) were consistent with the predictive phenotypes. Conclusion In this study, we identified the mutation spectrum of CYP21A2 gene in Chinese patients, especially the younger age cohort in pediatrics. Micro‐conversions were the most popular mutations. Moreover, the genotypes and phenotypes were well correlated in this cohort of salt wasting 21‐OHD recruited from neonatal intensive care unit.https://doi.org/10.1002/mgg3.15012 l‐hydroxylase deficiencycongenital adrenal hyperplasiaCYP21A2 genegenotypephenotype |
| spellingShingle | Yang Liu Jie Zheng Nan Liu Xiaowei Xu Xinjie Zhang Ying Zhang Guoxu Li Geli Liu Chunquan Cai Jianbo Shu The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohort Molecular Genetics & Genomic Medicine 2 l‐hydroxylase deficiency congenital adrenal hyperplasia CYP21A2 gene genotype phenotype |
| title | The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohort |
| title_full | The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohort |
| title_fullStr | The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohort |
| title_full_unstemmed | The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohort |
| title_short | The spectrum of CYP21A2 gene mutations in patients with classic salt wasting form of 2l‐hydroxylase deficiency in a Chinese cohort |
| title_sort | spectrum of cyp21a2 gene mutations in patients with classic salt wasting form of 2l hydroxylase deficiency in a chinese cohort |
| topic | 2 l‐hydroxylase deficiency congenital adrenal hyperplasia CYP21A2 gene genotype phenotype |
| url | https://doi.org/10.1002/mgg3.1501 |
| work_keys_str_mv | AT yangliu thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT jiezheng thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT nanliu thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT xiaoweixu thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT xinjiezhang thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT yingzhang thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT guoxuli thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT geliliu thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT chunquancai thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT jianboshu thespectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT yangliu spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT jiezheng spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT nanliu spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT xiaoweixu spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT xinjiezhang spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT yingzhang spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT guoxuli spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT geliliu spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT chunquancai spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort AT jianboshu spectrumofcyp21a2genemutationsinpatientswithclassicsaltwastingformof2lhydroxylasedeficiencyinachinesecohort |