Scientists discover rare genetic defect which causes severe lung disease in children

A rare inherited condition which can lead to infant death through severe lung disease has been discovered by an international group of scientists, according to new research published in the Journal of Clinical Investigation. 

Researchers from the Genome Damage and Stability Centre, at the University of Sussex, working alongside the University Medical Center (Utrecht, Netherlands) and Baylor College of Medicine (Houston, USA) have identified ‘lung disease immunodeficiency chromosome breakage syndrome’ or LICS – an inherited syndrome that is associated with severe lung disease.

The study came about when Dr Jo Murray, from the University of Sussex, began working with the team from the Netherlands, to look at two baby girls from the same family who had both died of severe lung disease. The children had chromosome instability and were suffering from immunodeficiency, which had prevented their bodies from fighting infection.

Defects in a gene called NSMCE3 were thought to have caused the disease in both the Dutch children. By using a new online genetic ‘matching’ service called GeneMatcher the Sussex and the Netherlands researchers were able to team-up with the Baylor College of Medicine in the USA who were also studying the same NSMCE3 gene in an American family. The US family had also sadly lost two children to lung failure in early childhood and had mutations in the same gene.

Research teams from Sussex’s Genome Damage and Stability Centre, led by Dr Jo Murray, Professor Laurence Pearl and Dr Antony Oliver, discovered the problem in the children’s cells was caused specifically by a defect in the levels of Smc5/6 – a vital group of proteins that are needed for accurate copying and repair of DNA. 

Dr Jo Murray, who coordinated the study at Sussex’s Genome Damage and Stability Centre, said: “This international study shows that collaboration between clinicians and research scientists is key to understanding what is going on in the cells and to the development of diagnostics tools."

“The mutation we’ve discovered in the NSMCE3 gene is rare but mutations in related genes could lead to similar tragic outcomes – which is why it is so important that we now work to develop a clinical test that can be used to identify families at risk.”

Dr Gijs van Haaften, associate professor of genetics and leader of the group in Utrecht, the Netherlands said: “Now we can provide a scientific explanation to the families, hopefully improve diagnostic opportunities for future children with a similar disease and understand more of the function of the DNA repair complex in the human body in health and disease.” 

Dr Sharon Plon professor of pediatrics - oncology and molecular and human genetics at Baylor College of Medicine said: “This is a particularly good example of different groups doing genomic sequencing and individually not having enough data, but by sharing data achieving important results.”

Dr Deborah Ritter, research scientist of paediatrics at the Baylor and Texas Children’s Hospital, said of the American families decision to participate in the research: “I cannot say enough how highly I regard their decision to participate and what an impact it has had on understanding this syndrome better, or how often I thought of their families as this work developed. Even though I only ‘met’ their DNA, the parents and the children they lost were present to me.”

The study, which was funded by the Medical Research Council, is entitled: Destabilized SMC5-6 complex leads to chromosome breakage syndrome with severe lung disease”  and has been published on the Journal of Clinical Investigation's website.

By: Lynsey Ford
Last updated: Monday, 25 July 2016