Researchers identify fifth gene responsible for Joubert syndrome

An international study by researchers at Seattle Children’s Hospital Research Institute, the University of Washington School of Medicine, and Radboud University in Nijmegen, Netherlands has identified a new genetic cause for Joubert syndrome (JS).

Joubert syndrome is an inherited condition that affects development of the cerebellum and brainstem, the structures in the brain that coordinate movements and regulate basic functions such as breathing, swallowing, heart rate and consciousness.

The study, published in the June 10, 2007 issue of Nature Genetics, confirms key information about the genetic changes that cause JS and cellular structures called cilia, conclusively placing JS in a class of recently identified ciliopathic conditions. Though the disease is statistically rare and four other genetic markers have been previously identified, researchers believe these findings are important.

Joubert syndrome can result in developmental delay, poor physical coordination, irregular breathing, visual impairment, kidney failure and extra digits. Diverse symptoms may occur making diagnosis difficult, though patients typically feature a characteristic configuration of the brainstem and cerebellum on magnetic resonance imaging (MRI), where the abnormally developed brain stem resembles the shape of a molar tooth. The researchers’ discovery of mutation in the gene (RPGRIP1L) now paves the way for definitive DNA testing that can more conclusively diagnose JS in some patients, and also identify asymptomatic carriers who might unknowingly pass the condition to their future children.

In addition to identifying a fifth gene for JS, the study also sheds light on the role of cilia in this disease and possibly others. Primary cilia are tiny projections on cell surfaces that allow the inside of cells to communicate with their outside environment. Recent research has found that defects in cilia function lead to various newly identified syndromes called ciliopathies. The paper describes a genetic change that prevents interaction between two particular cilia proteins, presumably disrupting cilia function and causing JS. This links JS to other diseases such as Leber congenital amaurosis, Senior-Loken syndrome and nephronophthisis, the most common genetic cause of kidney failure in children. All these conditions share disruptions in the protein networks of cilia. Further, this study exemplifies the power of international collaborative research, an increasingly important trend in biomedical discoveries.

Study findings add substantially to the way JS and other ciliopathies will be identified and understood. “By discovering this gene, we’re on the forefront of research changing how we think about brain, retina and kidney development,” said Dr. Dan Doherty, co-author on the study, from the Division of Genetics and Developmental Medicine at Seattle Children’s Hospital Research Institute. “These advances will lead to better understanding of both normal and abnormal brain development and eventually improved treatments for a variety of diseases.”

Source: Children's Hospital and Regional Medical Center of Seattle

Related stories:

Loss of cell's 'antenna' linked to cancer's development
Submarines have periscopes. Insects have antennae. And increasingly, biologists are finding that most normal vertebrate cells have cilia, small hair-like structures that protrude like antennae into the surrounding environment to detect signals that control cell growth. In a new study published in the June 29 issue of Cell, Fox Chase Cancer Center researchers describe the strong link between ciliary signaling and cancer and identify the rogue engineers responsible for dismantling the cell’s antenna.
Genetic defect links respiratory disease and congenital heart disease
The same genetic defect that causes a rare respiratory disease may also lead to some types of congenital heart disease, according to a study from the University of North Carolina at Chapel Hill School of Medicine.
Forsyth scientists gain greater understanding of how embryos differentiate left from right
Researchers at the Forsyth Institute have discovered a new mechanism responsible for early left/right patterning, the process by which organs locate themselves on the left or right side of the body. The discovery of this novel mechanism, garnered through the study of three different vertebrates (frogs, chickens and zebrafish), marks the first time that a single common mechanism has been identified in left-right patterning in three distinct species. Such a discovery may have far-reaching implications for the understanding of craniofacial development, right-left hand preference, right/left brain dominance and a variety of birth defects in humans.
Study shows a fundamental difference between how insects, mammals detect odors
When smelling their favorite foods, both humans and insects usually go with their instinct and try to find the source. However, according to new research by Leslie Vosshall and colleagues at Rockefeller University, when it comes to smell, that’s about the only thing that they have in common.
Genome of simplest animal reveals ancient lineage, confounding array of complex capabilities
As Aesop said, appearances are deceiving—even in life's tiniest critters. From first detection in the 1880s, clinging to the sides of an aquarium, to its recent characterization by the U.S. Department of Energy Joint Genome Institute (DOE JGI), a simple and primitive animal, Trichoplax adhaerens, appears to harbor a far more complex suite of capabilities than meets the eye. The findings, reported in the August 21 online edition of the journal Nature, establish a group of organisms as a branching point of animal evolution and identify sets of genes, or a "parts list," employed by organisms that have evolved along particular branches.
Scientists identify critical protein complex in formation of cell cilia
An international team led by NYU Cancer Institute have identified a protein complex that regulates the formation of cilia, which are found on virtually all mature human cells and are essential to normal cell function.
Bacterial pneumonia caused most deaths in 1918 influenza pandemic
The majority of deaths during the influenza pandemic of 1918-1919 were not caused by the influenza virus acting alone, report researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Instead, most victims succumbed to bacterial pneumonia following influenza virus infection. The pneumonia was caused when bacteria that normally inhabit the nose and throat invaded the lungs along a pathway created when the virus destroyed the cells that line the bronchial tubes and lungs.
St. Jude finds 'dancing' hair cells are key to humans' acute hearing
St. Jude Children's Research Hospital investigators have found that an electrically powered amplification mechanism in the cochlea of the ear is critical to the acute hearing of humans and other mammals. The findings will enable better understanding of how hearing loss can result from malfunction of this amplification machinery due to genetic mutation or overdose of drugs such as aspirin.

News discussion:

Medicine & Health news