Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum.

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.

Concentrations and distributions of 18 organochlorine pesticides listed in the Stockholm Convention in surface sediments from the Liaohe River basin, China.

Organochlorine pesticides (OCPs) were analyzed in 26 surface sediment samples from the Liaohe River basin, and the distributions of and potential environmental risks posed by OCPs in the basin were evaluated. Eighteen OCPs listed in the Stockholm Convention were determined using isotope-dilution gas chromatography-high resolution mass spectrometry. This is the first study of hexachlorobenzene (HCB) in the Liaohe River basin sediments. The total OCP concentrations were 0.39-68.06 ng g(-1) dry weight. The total α-, ß-, γ-, and δ-hexachlorocyclohexane (HCH), the total dichlorodiphenyltrichloroethane (DDT - p,p'-dichlorodiphenyldichloroethane (DDD), p,p'-dichlorodiphenyldichloroethylene (DDE), o,p(')-DDT, and p,p'-DDT), and the HCB concentrations in the sediment samples were 0.1-28.48 ng g(-1) (mean 4.01 ng g(-1)), 0.08-6.52 ng g(-1) (mean 3.07 ng g(-1)), and 0.18-24.8 ng g(-1) (mean 4.38 ng g(-1)), respectively. The HCB concentrations were higher than the concentrations of the other OCPs, and the HCHs and HCB together were the dominant OCPs. ß-HCH was the most abundant HCH isomer. The concentrations of DDTs and other OCPs were relatively low, and the (DDE+DDD)/DDT ratios (>0.5) and DDD/DDE ratios (<1) indicated that no recent DDT inputs had occurred in the Liaohe River system. The main sources of HCHs were probably the historical production and agricultural use of HCH in the study area. The DDT and HCH concentrations were generally below or similar to the concentrations that have been found in other parts of the world. An ecotoxicological evaluation indicated that HCHs in surface sediments pose slight risks to human and ecological health in the Liaohe River basin.