PUBLICATION
Monoallelic Loss of Function BMP2 Variants Result in BMP2-Related Skeletal Dysplasia Spectrum
- Authors
- Priestley, J.R.C., Deshwar, A.R., Murthy, H., D'Agostino, M.D., Dupuis, L., Gangaram, B., Gray, C., Jobling, R., Pannia, E., Platzer, K., Prescott, K., Redman, M., Rippert, A.L., Rosenfeld, J.A., Scott, D.A., Wang, Y.W., Schmederer, Z., Dalal, A., Sarma, A.S., Skraban, C., Dowling, J.J., Mendoza-Londono, R., Slavotinek, A., Bhoj, E.J.
- ID
- ZDB-PUB-230501-45
- Date
- 2023
- Source
- Genetics in medicine : official journal of the American College of Medical Genetics 25(8): 100863 (Journal)
- Registered Authors
- Murthy, Harsha, Slavotinek, Anne
- Keywords
- BMP2, Bone morphogenic protein, multiple congenital anomalies, skeletal dysplasia
- MeSH Terms
-
- Animals
- Bone Morphogenetic Protein 2/genetics
- Bone Morphogenetic Proteins
- Cell Differentiation
- Humans
- Osteochondrodysplasias*
- Osteogenesis/genetics
- Retrospective Studies
- Zebrafish*/genetics
- PubMed
- 37125634 Full text @ Genet. Med.
Citation
Priestley, J.R.C., Deshwar, A.R., Murthy, H., D'Agostino, M.D., Dupuis, L., Gangaram, B., Gray, C., Jobling, R., Pannia, E., Platzer, K., Prescott, K., Redman, M., Rippert, A.L., Rosenfeld, J.A., Scott, D.A., Wang, Y.W., Schmederer, Z., Dalal, A., Sarma, A.S., Skraban, C., Dowling, J.J., Mendoza-Londono, R., Slavotinek, A., Bhoj, E.J. (2023) Monoallelic Loss of Function BMP2 Variants Result in BMP2-Related Skeletal Dysplasia Spectrum. Genetics in medicine : official journal of the American College of Medical Genetics. 25(8):100863.
Abstract
Purpose Bone morphogenic proteins (BMPs) regulate gene expression related to many critical developmental processes, including osteogenesis for which they are named. BMP2 is widely expressed in cells of mesenchymal origin, including bone, cartilage, skeletal and cardiac muscle, and adipose tissue. It also participates in neurodevelopment by inducing differentiation of neural stem cells. In humans, BMP2 variants result in a multiple congenital anomaly syndrome through a haploinsufficiency mechanism. We sought to expand the phenotypic spectrum and highlight phenotypes of patients harboring monoallelic missense variants in BMP2.
Methods We employed retrospective chart review to examine phenotypes from an international cohort of 18 individuals and compared these to published cases. Patient-derived missense variants were modeled in zebrafish to examine their effect on the ability of bmp2b to promote embryonic ventralization.
Results The presented cases recapitulated existing descriptions of BMP2-related disorder including craniofacial, cardiac, and skeletal anomalies and exhibit a wide phenotypic spectrum. We also identified patients with neural tube defects, structural brain anomalies, and endocrinopathies. Missense variants modeled in zebrafish resulted in loss of protein function.
Conclusions We use this expansion of reported phenotypes to suggest multidisciplinary medical monitoring and management of patients with BMP2-related skeletal dysplasia spectrum.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping