Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center Cohort
Objective:The aim of this study was the molecular characterization of the AR gene as the cause of 46,XY disorder in our population.Methods:We studied 41, non related, 46,XY disorder of sexual differentiation index cases, having characteristics consistent with androgen insensivity syndrome (AIS). Gen...
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| Format: | Article |
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Galenos Yayincilik
2019-03-01
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| Series: | JCRPE |
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http://www.jcrpe.org/archives/archive-detail/article-preview/androgen-nsensitivity-syndrome-clinical-phenotype-/19687
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| _version_ | 1797923500035407872 |
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| author | Maria Sol Touzon Natalia Perez Garrido Roxana Marino Pablo Ramirez Mariana Costanzo Gabriela Guercio Esperanza Berensztein Marco A. Rivarola Alicia Belgorosky |
| author_facet | Maria Sol Touzon Natalia Perez Garrido Roxana Marino Pablo Ramirez Mariana Costanzo Gabriela Guercio Esperanza Berensztein Marco A. Rivarola Alicia Belgorosky |
| author_sort | Maria Sol Touzon |
| collection | DOAJ |
| description | Objective:The aim of this study was the molecular characterization of the AR gene as the cause of 46,XY disorder in our population.Methods:We studied 41, non related, 46,XY disorder of sexual differentiation index cases, having characteristics consistent with androgen insensivity syndrome (AIS). Genomic DNA was isolated from peripheral blood leukocytes of all patients and 25 family members from 17 non-related families.Results:The AR gene analysis revealed an abnormal sequence in 58.5% of the index patients. All of the complete AIS (CAIS) cases were genetically confirmed, while in the partial form (PAIS) a mutation in AR was detected in only 13 (43.3%). Molecular studies revealed other affected or carrier relatives in 87% of the index cases. The AR mutations were found spread along the whole coding sequence, with a higher prevalence in the ligand binding domain. Nine out of 23 (39%) AR mutations were novel. In 17% of patients with detected AR mutations, somatic mosaicism was detected in leucocyte DNA. In our cohort, long-term follow up gender dysphoria, raised as male or female, was not found. Finally, in suspected PAIS, the identification of AR mutation occurred significantly less than in CAIS patients.Conclusion:Improved knowledge of the components of the AR complex and signaling network might contribute to long term outcome and genetic counseling in AIS patients. |
| first_indexed | 2024-04-10T14:47:14Z |
| format | Article |
| id | doaj.art-c6602376e5884b39b76c135a2b3fd8fe |
| institution | Directory Open Access Journal |
| issn | 1308-5727 1308-5735 |
| language | English |
| last_indexed | 2024-04-10T14:47:14Z |
| publishDate | 2019-03-01 |
| publisher | Galenos Yayincilik |
| record_format | Article |
| series | JCRPE |
| spelling | doaj.art-c6602376e5884b39b76c135a2b3fd8fe2023-02-15T16:07:47ZengGalenos YayincilikJCRPE1308-57271308-57352019-03-01111243310.4274/jcrpe.galenos.2018.2018.018513049054Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center CohortMaria Sol Touzon0Natalia Perez Garrido1Roxana Marino2Pablo Ramirez3Mariana Costanzo4Gabriela Guercio5Esperanza Berensztein6Marco A. Rivarola7Alicia Belgorosky8 Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Hospital de Pediatria Garrahan, Endocrinology Service, Buenos Aires, Argentina Objective:The aim of this study was the molecular characterization of the AR gene as the cause of 46,XY disorder in our population.Methods:We studied 41, non related, 46,XY disorder of sexual differentiation index cases, having characteristics consistent with androgen insensivity syndrome (AIS). Genomic DNA was isolated from peripheral blood leukocytes of all patients and 25 family members from 17 non-related families.Results:The AR gene analysis revealed an abnormal sequence in 58.5% of the index patients. All of the complete AIS (CAIS) cases were genetically confirmed, while in the partial form (PAIS) a mutation in AR was detected in only 13 (43.3%). Molecular studies revealed other affected or carrier relatives in 87% of the index cases. The AR mutations were found spread along the whole coding sequence, with a higher prevalence in the ligand binding domain. Nine out of 23 (39%) AR mutations were novel. In 17% of patients with detected AR mutations, somatic mosaicism was detected in leucocyte DNA. In our cohort, long-term follow up gender dysphoria, raised as male or female, was not found. Finally, in suspected PAIS, the identification of AR mutation occurred significantly less than in CAIS patients.Conclusion:Improved knowledge of the components of the AR complex and signaling network might contribute to long term outcome and genetic counseling in AIS patients. http://www.jcrpe.org/archives/archive-detail/article-preview/androgen-nsensitivity-syndrome-clinical-phenotype-/19687 46XY disorders of sex developmentandrogen insensitivity syndromeandrogen receptor gene mutationsmosaicismclinical phenotype |
| spellingShingle | Maria Sol Touzon Natalia Perez Garrido Roxana Marino Pablo Ramirez Mariana Costanzo Gabriela Guercio Esperanza Berensztein Marco A. Rivarola Alicia Belgorosky Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center Cohort JCRPE 46 XY disorders of sex development androgen insensitivity syndrome androgen receptor gene mutations mosaicism clinical phenotype |
| title | Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center Cohort |
| title_full | Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center Cohort |
| title_fullStr | Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center Cohort |
| title_full_unstemmed | Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center Cohort |
| title_short | Androgen Insensitivity Syndrome: Clinical Phenotype and Molecular Analysis in a Single Tertiary Center Cohort |
| title_sort | androgen insensitivity syndrome clinical phenotype and molecular analysis in a single tertiary center cohort |
| topic | 46 XY disorders of sex development androgen insensitivity syndrome androgen receptor gene mutations mosaicism clinical phenotype |
| url |
http://www.jcrpe.org/archives/archive-detail/article-preview/androgen-nsensitivity-syndrome-clinical-phenotype-/19687
|
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