Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome
22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes, involving ∼3 Mb of DNA. In a relatively large population of a Brazilian 22q11.2DS cohort (60 patients), we investigated genetic variant...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Genetics Research |
| Online Access: | http://dx.doi.org/10.1155/2024/5549592 |
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| author | Natalia Nunes Beatriz Carvalho Nunes Malú Zamariolli Diogo Cordeiro de Queiroz Soares Leonardo Caires dos Santos Anelisa Gollo Dantas Vera Ayres Meloni Sintia Iole Belangero Vera Lúcia Gil-Da-Silva-Lopes Chong Ae Kim Maria Isabel Melaragno |
| author_facet | Natalia Nunes Beatriz Carvalho Nunes Malú Zamariolli Diogo Cordeiro de Queiroz Soares Leonardo Caires dos Santos Anelisa Gollo Dantas Vera Ayres Meloni Sintia Iole Belangero Vera Lúcia Gil-Da-Silva-Lopes Chong Ae Kim Maria Isabel Melaragno |
| author_sort | Natalia Nunes |
| collection | DOAJ |
| description | 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes, involving ∼3 Mb of DNA. In a relatively large population of a Brazilian 22q11.2DS cohort (60 patients), we investigated genetic variants that could act as genetic modifiers and contribute to the phenotypic heterogeneity, using a targeted NGS (Next Generation Sequencing) with a specific Ion AmpliSeq panel to sequence nine candidate genes (CRKL, MAPK1, HIRA, TANGO2, PI4KA, HDAC1, ZDHHC8, ZFPM2, and JAM3), mapped in and outside the 22q11.2 hemizygous deleted region. In silico prediction was performed, and the whole-genome sequencing annotation analysis package (WGSA) was used to predict the possible pathogenic effect of single nucleotide variants (SNVs). For the in silico prediction of the indels, we used the genomic variants filtered by a deep learning model in NGS (GARFIELD-NGS). We identified six variants, 4 SNVs and 2 indels, in MAPK1, JAM3, and ZFPM2 genes with possibly synergistic deleterious effects in the context of the 22q11.2 deletion. Our results provide the opportunity for the discovery of the co-occurrence of genetic variants with 22q11.2 deletions, which may influence the patients´ phenotype. |
| format | Article |
| id | doaj-art-3aec9cf7c8f64a16aa4b81645a566b72 |
| institution | OA Journals |
| issn | 1469-5073 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Genetics Research |
| spelling | doaj-art-3aec9cf7c8f64a16aa4b81645a566b722025-08-20T02:16:22ZengWileyGenetics Research1469-50732024-01-01202410.1155/2024/5549592Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion SyndromeNatalia Nunes0Beatriz Carvalho Nunes1Malú Zamariolli2Diogo Cordeiro de Queiroz Soares3Leonardo Caires dos Santos4Anelisa Gollo Dantas5Vera Ayres Meloni6Sintia Iole Belangero7Vera Lúcia Gil-Da-Silva-Lopes8Chong Ae Kim9Maria Isabel Melaragno10Genetics DivisionGenetics DivisionGenetics DivisionGenetics UnitGenetics DivisionGenetics DivisionGenetics DivisionGenetics DivisionDepartment of Translational MedicineGenetics UnitGenetics Division22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes, involving ∼3 Mb of DNA. In a relatively large population of a Brazilian 22q11.2DS cohort (60 patients), we investigated genetic variants that could act as genetic modifiers and contribute to the phenotypic heterogeneity, using a targeted NGS (Next Generation Sequencing) with a specific Ion AmpliSeq panel to sequence nine candidate genes (CRKL, MAPK1, HIRA, TANGO2, PI4KA, HDAC1, ZDHHC8, ZFPM2, and JAM3), mapped in and outside the 22q11.2 hemizygous deleted region. In silico prediction was performed, and the whole-genome sequencing annotation analysis package (WGSA) was used to predict the possible pathogenic effect of single nucleotide variants (SNVs). For the in silico prediction of the indels, we used the genomic variants filtered by a deep learning model in NGS (GARFIELD-NGS). We identified six variants, 4 SNVs and 2 indels, in MAPK1, JAM3, and ZFPM2 genes with possibly synergistic deleterious effects in the context of the 22q11.2 deletion. Our results provide the opportunity for the discovery of the co-occurrence of genetic variants with 22q11.2 deletions, which may influence the patients´ phenotype.http://dx.doi.org/10.1155/2024/5549592 |
| spellingShingle | Natalia Nunes Beatriz Carvalho Nunes Malú Zamariolli Diogo Cordeiro de Queiroz Soares Leonardo Caires dos Santos Anelisa Gollo Dantas Vera Ayres Meloni Sintia Iole Belangero Vera Lúcia Gil-Da-Silva-Lopes Chong Ae Kim Maria Isabel Melaragno Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome Genetics Research |
| title | Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome |
| title_full | Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome |
| title_fullStr | Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome |
| title_full_unstemmed | Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome |
| title_short | Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome |
| title_sort | variants in candidate genes for phenotype heterogeneity in patients with the 22q11 2 deletion syndrome |
| url | http://dx.doi.org/10.1155/2024/5549592 |
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