Clinical Significance of De Novo and Inherited Copy-Number Variation
Copy-number variations (CNVs) are a common cause of intellectual disability and/or multiple congenital anomalies (ID/MCA). However, the clinical interpretation of CNVs remains challenging, especially for inherited CNVs. Well-phenotyped patients (5,531) with ID/MCA were screened for rare CNVs using a...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1826290389035778048 |
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| author | Vulto-van Silfhout, A Hehir-Kwa, J van Bon, B Schuurs-Hoeijmakers, J Meader, S Hellebrekers, C Thoonen, I de Brouwer, A Brunner, H Webber, C Pfundt, R de Leeuw, N De Vries, B |
| author_facet | Vulto-van Silfhout, A Hehir-Kwa, J van Bon, B Schuurs-Hoeijmakers, J Meader, S Hellebrekers, C Thoonen, I de Brouwer, A Brunner, H Webber, C Pfundt, R de Leeuw, N De Vries, B |
| author_sort | Vulto-van Silfhout, A |
| collection | OXFORD |
| description | Copy-number variations (CNVs) are a common cause of intellectual disability and/or multiple congenital anomalies (ID/MCA). However, the clinical interpretation of CNVs remains challenging, especially for inherited CNVs. Well-phenotyped patients (5,531) with ID/MCA were screened for rare CNVs using a 250K single-nucleotide polymorphism array platform in order to improve the understanding of the contribution of CNVs to a patients phenotype. We detected 1,663 rare CNVs in 1,388 patients (25.1%; range 0-5 per patient) of which 437 occurred de novo and 638 were inherited. The detected CNVs were analyzed for various characteristics, gene content, and genotype-phenotype correlations. Patients with severe phenotypes, including organ malformations, had more de novo CNVs (P < 0.001), whereas patient groups with milder phenotypes, such as facial dysmorphisms, were enriched for both de novo and inherited CNVs (P < 0.001), indicating that not only de novo but also inherited CNVs can be associated with a clinically relevant phenotype. Moreover, patients with multiple CNVs presented with a more severe phenotype than patients with a single CNV (P < 0.001), pointing to a combinatorial effect of the additional CNVs. In addition, we identified 20 de novo single-gene CNVs that directly indicate novel genes for ID/MCA, including ZFHX4, ANKH, DLG2, MPP7, CEP89, TRIO, ASTN2, and PIK3C3. © 2013 WILEY PERIODICALS, INC. |
| first_indexed | 2024-03-07T02:43:27Z |
| format | Journal article |
| id | oxford-uuid:ab3aaf56-4323-4652-8157-1b65da9441a9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:43:27Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:ab3aaf56-4323-4652-8157-1b65da9441a92022-03-27T03:20:39ZClinical Significance of De Novo and Inherited Copy-Number VariationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ab3aaf56-4323-4652-8157-1b65da9441a9EnglishSymplectic Elements at Oxford2013Vulto-van Silfhout, AHehir-Kwa, Jvan Bon, BSchuurs-Hoeijmakers, JMeader, SHellebrekers, CThoonen, Ide Brouwer, ABrunner, HWebber, CPfundt, Rde Leeuw, NDe Vries, BCopy-number variations (CNVs) are a common cause of intellectual disability and/or multiple congenital anomalies (ID/MCA). However, the clinical interpretation of CNVs remains challenging, especially for inherited CNVs. Well-phenotyped patients (5,531) with ID/MCA were screened for rare CNVs using a 250K single-nucleotide polymorphism array platform in order to improve the understanding of the contribution of CNVs to a patients phenotype. We detected 1,663 rare CNVs in 1,388 patients (25.1%; range 0-5 per patient) of which 437 occurred de novo and 638 were inherited. The detected CNVs were analyzed for various characteristics, gene content, and genotype-phenotype correlations. Patients with severe phenotypes, including organ malformations, had more de novo CNVs (P < 0.001), whereas patient groups with milder phenotypes, such as facial dysmorphisms, were enriched for both de novo and inherited CNVs (P < 0.001), indicating that not only de novo but also inherited CNVs can be associated with a clinically relevant phenotype. Moreover, patients with multiple CNVs presented with a more severe phenotype than patients with a single CNV (P < 0.001), pointing to a combinatorial effect of the additional CNVs. In addition, we identified 20 de novo single-gene CNVs that directly indicate novel genes for ID/MCA, including ZFHX4, ANKH, DLG2, MPP7, CEP89, TRIO, ASTN2, and PIK3C3. © 2013 WILEY PERIODICALS, INC. |
| spellingShingle | Vulto-van Silfhout, A Hehir-Kwa, J van Bon, B Schuurs-Hoeijmakers, J Meader, S Hellebrekers, C Thoonen, I de Brouwer, A Brunner, H Webber, C Pfundt, R de Leeuw, N De Vries, B Clinical Significance of De Novo and Inherited Copy-Number Variation |
| title | Clinical Significance of De Novo and Inherited Copy-Number Variation |
| title_full | Clinical Significance of De Novo and Inherited Copy-Number Variation |
| title_fullStr | Clinical Significance of De Novo and Inherited Copy-Number Variation |
| title_full_unstemmed | Clinical Significance of De Novo and Inherited Copy-Number Variation |
| title_short | Clinical Significance of De Novo and Inherited Copy-Number Variation |
| title_sort | clinical significance of de novo and inherited copy number variation |
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