Monoallelic BMP2 Variants Predicted to Result in Haploinsufficiency Cause Craniofacial, Skeletal, and Cardiac Features Overlapping Those of 20p12 Deletions
Yang Tan Tiong, Claudia Gonzaga-Jauregui, Elizabeth J Bhoj, Kevin A Strauss, Karlla Brigatti, Erik Puffenberger, Dong Li, LiQin Xie, Nanditha Das, Ioanna Skubas, Ron A Deckelbaum, Virginia Hughes, Susannah Brydges, Sarah Hatsell, Chia-Jen Siao, Melissa G Dominguez, Aris Economides, John D Overton, Valerie Mayne, Peter J Simm Show all
AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2017
Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene superfamily encoding TGF-β-signaling proteins involved in bone and cartilage biology. Monoallelic deletions of 20p12 are variably associated with cleft palate, short stature, and developmental delay. Here, we report a cranioskeletal phenotype due to monoallelic truncating and frameshift BMP2 variants and deletions in 12 individuals from eight unrelated families that share features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inher..View full abstract
The authors thank the affected individuals and all family members for participating in this research. This research was supported by an internal grant from the Murdoch Children's Research Institute Cell Biology Theme. The Murdoch Children's Research Institute receives funding from the Victorian State Government through the Operational Infrastructure Support Program. A.R. was supported by radiz - Rare Disease Initiative Zurich, the Clinical Research Priority Program for Rare Diseases at the University of Zurich. We thank Bernard Drew, Trent Burgess, Juliane Gohlke, and Beate Kootz for technical support.