Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development
Background: Cytogenomic methods have gained space in the clinical investigation of patients with disorders/differences in sexual development (DSD). Here we evaluated the role of the SNP array in achieving a molecular diagnosis in Brazilian patients with syndromic DSD of unknown etiology. Methods: Tw...
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MDPI AG
2023-06-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/13/2235 |
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| author | José Antonio Diniz Faria Daniela R. Moraes Leslie Domenici Kulikowski Rafael Loch Batista Nathalia Lisboa Gomes Mirian Yumie Nishi Evelin Zanardo Carolina Kymie Vasques Nonaka Bruno Solano de Freitas Souza Berenice Bilharinho Mendonca Sorahia Domenice |
| author_facet | José Antonio Diniz Faria Daniela R. Moraes Leslie Domenici Kulikowski Rafael Loch Batista Nathalia Lisboa Gomes Mirian Yumie Nishi Evelin Zanardo Carolina Kymie Vasques Nonaka Bruno Solano de Freitas Souza Berenice Bilharinho Mendonca Sorahia Domenice |
| author_sort | José Antonio Diniz Faria |
| collection | DOAJ |
| description | Background: Cytogenomic methods have gained space in the clinical investigation of patients with disorders/differences in sexual development (DSD). Here we evaluated the role of the SNP array in achieving a molecular diagnosis in Brazilian patients with syndromic DSD of unknown etiology. Methods: Twenty-two patients with DSD and syndromic features were included in the study and underwent SNP-array analysis. Results: In two patients, the diagnosis of 46,XX <i>SRY +</i> DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and a 13q33.1 deletion encompassing the <i>FGFR2</i> and the <i>EFNB2</i> gene, were associated with genital atypia and syndromic characteristics in two patients with 46,XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7 Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataracts, a 12 Kb deletion on chromosome 10 was found, partially clarifying the syndromic phenotype, but not the genital atypia. Conclusions: The SNP array is a useful tool for DSD patients, identifying the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD. |
| first_indexed | 2024-03-11T01:44:24Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T01:44:24Z |
| publishDate | 2023-06-01 |
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| series | Diagnostics |
| spelling | doaj.art-b32db0017fb14b7bab0f56bf25c897042023-11-18T16:21:55ZengMDPI AGDiagnostics2075-44182023-06-011313223510.3390/diagnostics13132235Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual DevelopmentJosé Antonio Diniz Faria0Daniela R. Moraes1Leslie Domenici Kulikowski2Rafael Loch Batista3Nathalia Lisboa Gomes4Mirian Yumie Nishi5Evelin Zanardo6Carolina Kymie Vasques Nonaka7Bruno Solano de Freitas Souza8Berenice Bilharinho Mendonca9Sorahia Domenice10Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-909, BrazilUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilLaboratório de Citogenômica e Patologia Molecular LIM/03, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilLaboratório de Citogenômica e Patologia Molecular LIM/03, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilCentro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador 41253-190, BrazilCentro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador 41253-190, BrazilUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, BrazilBackground: Cytogenomic methods have gained space in the clinical investigation of patients with disorders/differences in sexual development (DSD). Here we evaluated the role of the SNP array in achieving a molecular diagnosis in Brazilian patients with syndromic DSD of unknown etiology. Methods: Twenty-two patients with DSD and syndromic features were included in the study and underwent SNP-array analysis. Results: In two patients, the diagnosis of 46,XX <i>SRY +</i> DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and a 13q33.1 deletion encompassing the <i>FGFR2</i> and the <i>EFNB2</i> gene, were associated with genital atypia and syndromic characteristics in two patients with 46,XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7 Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataracts, a 12 Kb deletion on chromosome 10 was found, partially clarifying the syndromic phenotype, but not the genital atypia. Conclusions: The SNP array is a useful tool for DSD patients, identifying the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD.https://www.mdpi.com/2075-4418/13/13/2235disorders of sexual developmentcopy number variationSNP array |
| spellingShingle | José Antonio Diniz Faria Daniela R. Moraes Leslie Domenici Kulikowski Rafael Loch Batista Nathalia Lisboa Gomes Mirian Yumie Nishi Evelin Zanardo Carolina Kymie Vasques Nonaka Bruno Solano de Freitas Souza Berenice Bilharinho Mendonca Sorahia Domenice Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development Diagnostics disorders of sexual development copy number variation SNP array |
| title | Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development |
| title_full | Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development |
| title_fullStr | Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development |
| title_full_unstemmed | Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development |
| title_short | Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development |
| title_sort | cytogenomic investigation of syndromic brazilian patients with differences of sexual development |
| topic | disorders of sexual development copy number variation SNP array |
| url | https://www.mdpi.com/2075-4418/13/13/2235 |
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