Scientists have identified a single mutated gene¹ that causes Hajdu-Cheney syndrome²（综合症） , a disorder³ of the bones causing progressive bone loss and osteoporosis（骨质疏松症） (fragile bones). The study, published in Nature Genetics today, gives vital insight into possible causes of osteoporosis and highlights the gene as a potential target for treating the condition. There are only 50 reported cases of Hajdu-Cheney syndrome (HCS), of which severe osteoporosis is a main feature. Osteoporosis is a condition leading to reduction in bone strength and susceptibility to fractures. It is the most common bone disease, with one in two women and one in five men over 50 in the UK fracturing a bone because of the condition. This represents a major public health problem yet, until this study, possible genetic⁴ causes of osteoporosis were poorly understood.

The team of scientists, led by the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) at King's College London and Guy's and St Thomas', set out to investigate the genetic cause of HCS in order to detect clues to the role genes⁵ might play in triggering osteoporosis.

Using a cutting edge technique for identifying disease-causing genes, known as exome sequencing（外显子组测序） , the team were able to identify NOTCH2 as the causative gene using DNA⁶ from just three unrelated HCS patients. The team then confirmed their findings in an additional 12 affected⁷ families, 11 of whom had an alteration⁸ in the identical portion of the same gene.

Professor Richard Trembath, Head of King's College London's Division of Genetics and Molecular⁹ Medicine and Medicine Director of the NIHR BRC, said: "Up until now, we knew very little about the genetic mechanisms¹⁰ of severe bone disease. But these findings add to our understanding of the uncommon¹¹ condition of HCS and provide an important basis to develop future studies in more common forms of osteoporosis, including the development of potential new therapies."