Study into the role of genetic variation in NPR3 in the regulation of endochondral bone formation and bone growth.

Previous to this study, we identified using whole exome sequencing the first two human mutations in NPR3 in two boys with peculiar phenotype marked by tall stature, arachnodactyly, hypotonia and hyperlaxity of the joints among other features. Based on in silico analysis using SNP databases and prediction programs and based on the available literature regarding NPR3 and the natriuretic signalling pathway, we are convinced that the identified variants are the disease causing variants. However, the exact mechanism whereby the identified mutations result in the observed phenotype remains unknown. During this project, we aim to increase the knowledge on NPR3 and its role in the regulation of bone growth by studying the functional effect of the identified variants in different in vitro assays as well as by screening additional samples with an abnormal growth in height. We are convinced that with the proposed experiments, we will be able to increase the insights on the role of the natriuretic signalling pathway in the regulation of bone growth.

Keywords:HEREDITARY, HUMAN HEIGHT, CELL CULTURES, MUTATION SCREENING

Disciplines:Genetics, Systems biology, Molecular and cell biology, Orthopaedics