20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits
Open accessAbstract
BACKGROUND: Wolff-Parkinson-White syndrome (WPW) is a bypass re-entrant 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) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. METHODS AND RESULTS: Using the array comparative genomic hybridisation (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 harboured 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 characterised 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.
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A novel form of Wolff-Parkinson-White syndrome is associated with microdeletion in the region of gene BMP2, which affects development of the annulus fibrosus.
“A novel form of WPW syndrome is associated with microdeletion in the region of gene BMP2, that encodes the bone morphogenetic protein-2, a member of the transforming growth factor (TGF-b) gene superfamily, and affects the development of annulus fibrosus.432”
From European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE) (2017) · cites this paper as [432]
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- Authors
- Lalani, S. R., Thakuria, J. V., Cox, G. F., Wang, X., Bi, W., Bray, M. S., Shaw, C., Cheung, S. W., Chinault, A. C., Boggs, B. A., Ou, Z., Brundage, E. K., Lupski, J. R., Gentile, J., Waisbren, S., Pursley, A., Ma, L., Khajavi, M., Zapata, G., Friedman, R., Kim, J. J., Towbin, J. A., Stankiewicz, P., Schnittger, S., Hansmann, I., Ai, T., Sood, S., Wehrens, X. H., Martin, J. F., Belmont, J. W., & Potocki, L.
- Affiliations
- Baylor College of Medicine (US)
- Boston Children's Hospital (US)
- The University of Texas Health Science Center at Houston (US)
- Munich Leukemia Laboratory (Germany) (DE)
- Martin Luther University Halle-Wittenberg (DE)
- Corresponding author
- Lalani, S R
- ORCID
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2008-09-23
- Volume
- 46
- Issue
- 3
- Pages
- 168-175
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC2680125
- OpenAlex
- W2093238929
- Cited by
- 108
- References
- 32
- Citations by year
- 2026: 1 · 2025: 6 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 9 · 2012: 6
- FWCI
- 10.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Medical Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01hl091771-04)
- National Heart, Lung, and Blood Institute (R01-HL091771)
- National Institute of Dental and Craniofacial Research (R01DE/HD 12324-12, R01DE012324)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- Wolff-Parkinson-White syndrome, BMP-2, JAG1, Alagille syndrome, dysmorphic features, de novo copy number variants, BMP signaling, preexcitation, PRKAG2
- MeSH terms
- Serrate-Jagged Proteins, Jagged-1 Protein, Adult, Animals, Calcium-Binding Proteins, Cognition Disorders, Electrocardiography, Female, Humans, Infant, Male, Membrane Proteins, Mice, Transgenic, Wolff-Parkinson-White Syndrome, Alagille Syndrome, Sequence Deletion, Gene Dosage, Facies, Oligonucleotide Array Sequence Analysis, Intercellular Signaling Peptides and Proteins, Mice, Comparative Genomic Hybridization, Bone Morphogenetic Protein 2
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