20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits
| Autor: | J. R. Lupski, Xueqing Wang, Seema R. Lalani, Zhishuo Ou, Richard A. Friedman, Jennifer K. Gentile, J. F. Martin, Tomohiko Ai, Amber N. Pursley, I. Hansmann, B. A. Boggs, A. C. Chinault, Gerald F. Cox, Pawel Stankiewicz, Gladys Zapata, Susan E. Waisbren, Jeffrey A. Towbin, Weimin Bi, Ellen K. Brundage, Mehrdad Khajavi, Chad A. Shaw, John W. Belmont, Jean J. Kim, S. Schnittger, Sau Wai Cheung, L. Ma, Subeena Sood, Lorraine Potocki, Joseph V. Thakuria, Molly S. Bray, Xander H.T. Wehrens |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male JAG1 Gene Dosage Cardiomyopathy Bone Morphogenetic Protein 2 Mice Transgenic Biology Gene dosage Article Electrocardiography Mice Alagille syndrome Genetics medicine Animals Humans Serrate-Jagged Proteins Genetics (clinical) Oligonucleotide Array Sequence Analysis Sequence Deletion Comparative Genomic Hybridization Calcium-Binding Proteins Hypertrophic cardiomyopathy Facies Infant Membrane Proteins medicine.disease Alagille Syndrome Intercellular Signaling Peptides and Proteins Jagged-1 Protein Female Wolff-Parkinson-White Syndrome Cognition Disorders Neurocognitive Comparative genomic hybridization |
| Zdroj: | Journal of Medical Genetics. 46:168-175 |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | Background: Wolff-Parkinson-White syndrome (WPW) is a bypass reentrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signaling in the development of annulus fibrosus in mice, it has been proposed that BMP signaling through the type 1a receptor and other downstream components may play a role in preexcitation. Methods and Results: Using the array comparative genomic hybridization (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these, harbored a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy-number variant in the Database of Genomic Variants and has not been identified in 13,321 individuals from other cohort examined by array CGH in our laboratory. Conclusions: Our findings demonstrate a novel genomic disorder characterized by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome. |
| Databáze: | OpenAIRE |
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