The work, co-led by geneticists at the University of Leeds, together with colleagues from institutes and universities in Paris, Rome and San Diego, should allow couples at risk of conceiving babies with the profoundly disabling Meckel-Gruber and Joubert syndromes to be identified beforehand through genetic screening.
Their findings, which show how the disease gene stops cells' finger-like antennae or 'cilia' from detecting and relaying information, may ultimately lead to treatments for more common related disorders, such as spina bifida and polycystic kidney disease. The paper is published in Nature Genetics today.
"By understanding the science behind this relatively rare condition, we can gain insight into other developmental conditions that are less serious but far more frequent," said University of Leeds researcher Professor Colin A. Johnson. "Spina bifida, for example, is one of the most common birth defects, affecting in one in every 1000 children."
Meckel-Gruber syndrome and Joubert syndrome are part of a wider family of disorders known as 'ciliopathies' – so-called because the cilia are not working as they should and do not respond properly to signals.
This lack of communication can prevent the neural tube from developing correctly in growing embryos, leading to abnormalities in the brain. Affected embryos can also develop abnormalities in the eyes, extra fingers or toes, and multiple cysts in their kidneys. These defects are often only picked up on a 12 week ultrasound scan.
To find the gene responsible for Meckel-Gruber and Joubert syndromes, the researchers examined DNA from families with a history of the disorder, from skin cells donated by patients, and from cells grown in the laboratory. They also studied zebrafish, which have very visible embryos.
The work identified a previously unknown gene – TMEM216 – as a cause of Meckel-Gruber and Joubert syndromes. They also showed that the faulty TMEM216 gene stopped cells from making a protein that is needed for signalling.
Because Meckel-Gruber and Joubert syndromes are recessive genetic disorders, only couples who both have a copy of the disease gene are at risk of conceiving babies with these birth defects.
The condition is more common in certain close-knit populations where the gene has been passed down from generation to generation. These include families of Ashkenazi Jewish origin.
"Accurate genetic testing for TMEM216 will be particularly important for families throughout the world that have a history of ciliopathies caused by mutations to this gene," said Professor Johnson.
"Now that we have identified a gene that causes Meckel-Gruber syndrome and Joubert syndrome, the role of particular signalling pathways whilst the embryo is developing can also be more clearly understood," he added.
Further information from: Paula Gould, University of Leeds press office: Tel 44 (0)113 343 8059, email firstname.lastname@example.org
Notes for editors
1. The paper, 'Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes', is published online in Nature Genetics (doi:10.1038/ng.594).
2. The work was jointly directed by Professor Colin Johnson (University of Leeds, UK), Dr Tania Attié-Bitach (Paris Descartes University and INSERM U781, Paris, France) and Professor Joseph Gleeson (University of California, San Diego School of Medicine, US).
3. One of the UK's largest medical, health and bioscience research bases, the University of Leeds delivers world leading research in medical engineering, cancer, cardiovascular studies, epidemiology, molecular genetics, musculoskeletal medicine, dentistry, psychology and applied health. Treatments and initiatives developed in Leeds are transforming the lives of people worldwide with conditions such as diabetes, HIV, tuberculosis and malaria. www.leeds.ac.uk
4. University of Leeds researchers received funding from the Sir Jules Thorn Charitable Trust (www.julesthorntrust.org.uk), the Medical Research Council (www.mrc.ac.uk) and the Newlife Foundation for Disabled Children (www.newlifecharity.co.uk).
5. The work was also supported by the Italian Ministry of Health, Telethon Foundation Italy, Pierfranco and Luisa Mariani Foundation, American Heart Association, l'Agence National pour la Recherche, National Institutes of Health, Burroughs Wellcome Fund, and Howard Hughes Medical Institute.
Paula Gould | EurekAlert!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences