Scientists Celebrate Genetic Breakthrough

Newswise — Scientists in Birmingham, England have made a genetic breakthrough in tracing the cause of a rare kidney and liver disorder. ARC syndrome* means babies are born with impairment to kidney and liver function, bleeding problems and weak muscles. This usually leads to early death. The gene which causes this condition has been identified.

The gene identified was not previously known to be involved in human disease - but was found in yeast. This discovery means children and adults can be tested to find out if they are carriers. If both parents are carriers, on average, there is a 1 in 4 chance of a child being born with ARC syndrome. These findings have been published in the Nature Genetics journal. Lead author Dr Paul Gissen works at the University of Birmingham and the Liver Unit, Birmingham Children's Hospital. His research fellowship is sponsored by charity Wellchild. Other experts collaborated from around the UK, Europe, Israel and Saudi Arabia.

Prof Eamonn Maher, head of Medical Genetics at the University of Birmingham explains the impact of this study: "We are excited to isolate the cause of this awful disease. This research is front-end molecular biology that sheds light on the genetic basis of diseases. This will impact on doctors seeking understand the causes of these conditions; and will lead to better information and testing for those families affected by this disorder".

Professor Deirdre Kelly, Head of Liver Unit at Birmingham Children's Hospital adds: "Hopefully the discovery of this new gene will not only increase understanding of how the disease develops, but will, eventually, provide hope of a treatment for affected infants."

It is hoped that successful research such as this is facilitated in future with the building of a new WellChild Centre in Birmingham. The centre will bring together the expertise of the University of Birmingham Medical School, the Institute of Child Health and Birmingham Children's Hospital.

Notes to Editor:* ARC syndrome is arthrogryposis - renal dysfunction - cholestasis (ARC) syndrome

To elucidate the molecular basis of ARC, the disease was mapped to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion6-9

The Department of Medical and Molecular Genetics is part of the Division of Reproductive and Child Health at the University of Birmingham's Medical School. The major interests of the Department are in human cancer biology, developmental genetics, molecular endocrinology and identification of recessive genes by autozygosity mapping.

The research was also supported by CLIMB (Children Living with Inherited Metabolic Diseases) charity; the Birmingham Children's Research Foundation and the Wellcome Trust.

WellChild is the UK's leading children's health charity. Established in 1977, they have funded major breakthroughs in child health affecting children in the UK and worldwide. Examples of support include the WellChild Neonatal Intensive Care Unit at King's College Hospital, London; cancer and diabetes projects at Princess Diana Children's Hospital, Birmingham; kidney research projects at Bristol Royal Children's Hospital, Bristol and the world's first pain research centre at Great Ormond Street Hospital, London.