For many years, scientists could not understand the mechanism of Williams (or Williams-Buren) syndrome, a rare genetic disease that affects an average of one in ten thousand newborns. American doctors have come close to solving the disease by creating its cellular model. The neurons in the syndrome are characterized by an increased number of dendrites and low viability. The article was published in the journal Nature.
People with Williams syndrome at different stages of life. Fig. from article N Engl J Med 2010; 362: 239-52. from the Williams Syndrome Association website.
People with Williams Syndrome (WS or WBS in English-language literature) have a characteristic appearance that resembles a folk elf with a low forehead, wide spread of eyebrows, a button nose, large mouth and sparse long teeth. That is why it is also called "the face of an elf".
Also, those suffering from this disease have reduced mental development while maintaining some intellectual abilities, in addition, they are distinguished by exceptional high sociability, friendliness, gullibility and good nature.
The syndrome was described in 1961 by New Zealand cardiologist John Cyprian Phipps Williams, famous for the fact that in 1969 he completely left his career, broke all ties and disappeared, appearing from time to time in Europe - the latest information about this amazing person dates back to 2000. Whether Williams, born in 1922, is still alive is unknown.
Past research has shown that Williams syndrome is associated with the deletion of a specific region from the long arm of the seventh chromosome. The missing fragment is about 3 million base pairs in length and affects 26 genes.
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However, with the notable exception of the elastin gene, the loss of which manifests itself in abnormal vascular wall formation, the functions of these genes remain largely unknown. Consequently, the mechanism of occurrence of the disease is not clear, which does not allow the creation of any effective methods of treatment.
A team of doctors from the University of California, San Diego, led by Alysson Muotri, selected five children with Williams syndrome between the ages of 8 and 14 years, confirmed their disease using genetic analysis, and took samples of somatic cells from the tissue of previously lost teeth.
Dental pulp cells, including neurons, are formed from a single stem cell line. Using Yamanaka's signaling protein factors, the authors of the work "returned" adult differentiated cells isolated from the pulp to such an early state. And then they started the process of turning into neurons and studied the characteristics of these cells.
It turned out that the "syndrome neurons" are anatomically and physiologically markedly different from normal. In particular, they have slowed growth and division and increased apoptosis. Neurons branch out into more dendrites than usual, and dendrites, in turn, have more spines. Thus, the tissue formed by these cells is characterized by extraordinary connectivity between cells and many synapses.
In addition, the scientists showed that the increased activity of apoptosis may be associated with one of the genes that have undergone the deletion, FZD9, a protein product of which is involved in the regulation of cell division. This was confirmed by experiments with disruption of the FZD9 function in a similar line of precursor cells of neurons obtained from pulp cells of healthy people.
"A new model using induced pluripotent stem cells fills the existing gap in the understanding of the cellular biology of Williams syndrome," the authors conclude, "and may bring new insights into the molecular mechanisms underlying disease and the work of the human social brain."
