An international team of researchers has identified two new genes connected with hereditary renal diseases.
The team of scientists from Canada, Germany, India, the Netherlands, Pakistan and the United States studied 850 proteins likely to be involved in 3 genetic ciliary diseases: nephronophthisis, Joubert syndrome and Meckel-Gruber syndrome. They mapped how these proteins interact to predict which of them play a crucial role in the diseases, something which led to the double gene discovery.
Ciliary diseases are caused by genetic defects to a part of the cell called the cilium. The cilium is crucial as it is involved with cell signalling pathways during cell development in different parts of the body. Cilia are protrusions of cells that have different functions: for example, cilia in the respiratory tract take care of transporting mucus, whereas cilia in the kidneys sense urine flow. Improper cilia development can result in various diseases.
However our knowledge of cilia composition, wiring, dynamics and the associated signalling pathways of the corresponding molecular building blocks and associated protein networks remains very limited.
Writing in the journal Cell, the team explains how they conducted their research on a family in Pakistan, in which four siblings had Joubert syndrome: they combined gene-mapping techniques with the use of a protein network map, thereby identifying the TCTN2 gene, which when defective, leads to onset of the condition. The syndrome occurs when a child receives the gene from each parent.
Joubert syndrome affects brain functioning and results in intellectual deficits, movement and coordination problems, and other symptoms such as kidney and eye problems. This syndrome is reported to affect approximately 1 in 100,000 children, although scientists believe this figure could be way off the mark since the disease could be affecting far more children worldwide.
So far, 10 genes have been connected with Joubert syndrome. One of the study authors from Canada’s Centre for Addiction and Mental Health previously discovered the CC2D2A gene, which accounts for about 9% of Joubert syndrome cases.
‘A defect in any aspect of this molecular pathway may have very similar effects at the clinical level,’ comments Dr John Vincent.
The other ciliopathy gene identified in this study – Atxn10 – leads to the condition called nephronophthisis, also associated with kidney and eye problems.
