An international research team has identified the gene responsible for Meckel-Gruber and Joubert Syndromes-inherited conditions that cause severe fetal abnormalities. The discovery may ultimately lead to treatments for more common related disorders, such as spina bifida and polycystic kidney disease.
The work, co-led by geneticists at the University of Leeds, England, 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 rather than waiting for a 12-week ultrasound as in the past. Their findings show how the disease gene stops cells’ finger-like antennae or “cilia” from detecting and relaying information. The study appears in the online version of the journal Nature Genetics.
“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,” Colin A. Johnson, University of Leeds professor and researcher, was quoted as saying. “Spina bifida, for example, is one of the most common birth defects, affecting one in every 1,000 children.”
Meckel-Gruber and Joubert syndromes, polycystic kidney disease, spina bifida, and many other genetic disorders are part of a wider family of disorders known as or suspected to be “ciliopathies”-so-called because the cilia are not working as they should and do not respond properly to signals. According to a University of Leeds press release, “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 the kidneys.”
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, and that the faulty TMEM216 gene stopped cells from making a protein that is needed for signaling, researchers noted.
Meckel-Gruber and Joubert syndromes are recessive genetic disorders. Only couples who both have a copy of the disease gene, and certain close-knit populations where the gene has been passed down from generation to generation, are at risk of conceiving babies with these birth defects.
“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,” Johnson said. “Now that we have identified a gene that causes Meckel-Gruber syndrome and Joubert syndrome, the role of particular signaling pathways whilst the embryo is developing can also be more clearly understood,” he added.
