A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome
Abstract Background Persistent Müllerian duct syndrome (PMDS) is defined as the presence of Müllerian duct derivatives in an otherwise normally virilized 46, XY male. It is usually caused by homozygous or compound heterozygous mutations in either the anti‐Müllerian hormone (AMH) or AMH receptor type...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-10-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1801 |
| _version_ | 1830282001389715456 |
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| author | Jianzheng Fang Gao Gao Jinyong Liu Lingbo Cai Yugui Cui Xiaoyu Yang |
| author_facet | Jianzheng Fang Gao Gao Jinyong Liu Lingbo Cai Yugui Cui Xiaoyu Yang |
| author_sort | Jianzheng Fang |
| collection | DOAJ |
| description | Abstract Background Persistent Müllerian duct syndrome (PMDS) is defined as the presence of Müllerian duct derivatives in an otherwise normally virilized 46, XY male. It is usually caused by homozygous or compound heterozygous mutations in either the anti‐Müllerian hormone (AMH) or AMH receptor type 2 (AMHR2) genes. The main purpose of the study is to determine the novel mutations of AMHR2 in PMDS patients and their intracytoplasmic sperm injection outcomes (ICSI). Methods Whole‐exome sequencing (WES) was carried out. Sanger sequencing was used to detect mutations in AMHR2. The pathogenicity of the identified variant and its possible effects on the protein were evaluated with in silico tools. The expression level of AMHR2 was determined by Western blotting. The spermatogenic function was evaluated by testicular sperm aspiration and histopathologic examination. The ICSI outcomes were recorded. Results We present two brothers with a history of bilateral cryptorchidism with orchidopexy and infertility due to azoospermia. A novel compound heterozygous mutation of c.1219C>T [p.R407X] and c.1387C>T [p.R463C] in exons 9 and 10 of AMHR2 (NM_020547.2) was detected by whole‐exome sequencing (WES). Spermatozoon could be retrieved from the two patients by testicular aspiration following intracytoplasmic sperm injection (ICSI) due to azoospermia. Finally, patient 1 had two healthy boys and patient 2 failed to conceive after three ICSI attempts. Conclusion The spermatozoa could obtain from PMDS patients due to azoospermia. For patients with bilateral cryptorchidism, PMDS should be included in the differential diagnosis and that genetic counseling needs to be considered when they seek reproductive help. |
| first_indexed | 2024-12-19T02:29:41Z |
| format | Article |
| id | doaj.art-62bdb091c8f64a2e938dd811d41609a5 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-19T02:29:41Z |
| publishDate | 2021-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-62bdb091c8f64a2e938dd811d41609a52022-12-21T20:39:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-10-01910n/an/a10.1002/mgg3.1801A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcomeJianzheng Fang0Gao Gao1Jinyong Liu2Lingbo Cai3Yugui Cui4Xiaoyu Yang5State Key Laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaThe Kangda College of Nanjing Medical University Nanjing ChinaState Key Laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaState Key Laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaState Key Laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaState Key Laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaAbstract Background Persistent Müllerian duct syndrome (PMDS) is defined as the presence of Müllerian duct derivatives in an otherwise normally virilized 46, XY male. It is usually caused by homozygous or compound heterozygous mutations in either the anti‐Müllerian hormone (AMH) or AMH receptor type 2 (AMHR2) genes. The main purpose of the study is to determine the novel mutations of AMHR2 in PMDS patients and their intracytoplasmic sperm injection outcomes (ICSI). Methods Whole‐exome sequencing (WES) was carried out. Sanger sequencing was used to detect mutations in AMHR2. The pathogenicity of the identified variant and its possible effects on the protein were evaluated with in silico tools. The expression level of AMHR2 was determined by Western blotting. The spermatogenic function was evaluated by testicular sperm aspiration and histopathologic examination. The ICSI outcomes were recorded. Results We present two brothers with a history of bilateral cryptorchidism with orchidopexy and infertility due to azoospermia. A novel compound heterozygous mutation of c.1219C>T [p.R407X] and c.1387C>T [p.R463C] in exons 9 and 10 of AMHR2 (NM_020547.2) was detected by whole‐exome sequencing (WES). Spermatozoon could be retrieved from the two patients by testicular aspiration following intracytoplasmic sperm injection (ICSI) due to azoospermia. Finally, patient 1 had two healthy boys and patient 2 failed to conceive after three ICSI attempts. Conclusion The spermatozoa could obtain from PMDS patients due to azoospermia. For patients with bilateral cryptorchidism, PMDS should be included in the differential diagnosis and that genetic counseling needs to be considered when they seek reproductive help.https://doi.org/10.1002/mgg3.1801AMH receptor type 2cryptorchidismintracytoplasmic sperm injection (ICSI)mutationPersistent Müllerian duct syndrome |
| spellingShingle | Jianzheng Fang Gao Gao Jinyong Liu Lingbo Cai Yugui Cui Xiaoyu Yang A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome Molecular Genetics & Genomic Medicine AMH receptor type 2 cryptorchidism intracytoplasmic sperm injection (ICSI) mutation Persistent Müllerian duct syndrome |
| title | A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome |
| title_full | A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome |
| title_fullStr | A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome |
| title_full_unstemmed | A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome |
| title_short | A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome |
| title_sort | novel mutation of amhr2 in two brothers with persistent mullerian duct syndrome and their intracytoplasmic sperm injection outcome |
| topic | AMH receptor type 2 cryptorchidism intracytoplasmic sperm injection (ICSI) mutation Persistent Müllerian duct syndrome |
| url | https://doi.org/10.1002/mgg3.1801 |
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