Genetics in medicine : official journal of the American College of Medical Genetics · 2023
Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Priestley Jessica R C, Deshwar Ashish R, Murthy Harsha, D'Agostino Maria D, Dupuis Lucie, Gangaram Balram, Gray Christopher, Jobling Rebekah, Pannia Emanuela, Platzer Konrad, Prescott Katrina, Redman Melody, Rippert Alyssa L, Rosenfeld Jill A, Scott Daryl A, Wang Yi W, Schmederer Zelia, Dalal Ashwin, Sarma Asodu S, Skraban Cara, Dowling James J, Mendoza-Londono Roberto, Slavotinek Anne, Bhoj Elizabeth J
Аннотация
PURPOSE: Bone morphogenic proteins (BMPs) regulate gene expression that is related to many critical developmental processes, including osteogenesis for which they are named. In addition, 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 used retrospective chart review to examine phenotypes from an international cohort of 18 individuals and compared these with 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 disorders, 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.
CONCLUSION: We use this expansion of reported phenotypes to suggest multidisciplinary medical monitoring and management of patients with BMP2-related skeletal dysplasia spectrum.
METHODS: We used retrospective chart review to examine phenotypes from an international cohort of 18 individuals and compared these with 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 disorders, 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.
CONCLUSION: We use this expansion of reported phenotypes to suggest multidisciplinary medical monitoring and management of patients with BMP2-related skeletal dysplasia spectrum.