Researchers at Hadassah University Medical Center on Jerusalem’s Mount Scopus have discovered the gene that causes primary ciliary dyskinesia (PCD), a rare inherited condition that affects functioning of the minute hairs (cilia) in the respiratory system and causes “transposition” of organs.

The discovery – by pediatrics branch chairman Prof. Eitan Kerem, Dr. David Shosayov, Dr. Malna Cohen and genetics department head Prof. Orly Elpeleg – focused on five children from two different families who suffer from PCD.

The doctors found that a mutation in the LRRC6 gene (leucine-rich repewat containing protein 6) caused the problem. They published their finding recently in PLoS One (Proceedings of the [US] Library of Science One). One of the results of the defect is repeated lung infections, sinusitis, frequent ear infections and fertility problems.

In about half of the cases, the mutation causes organs to develop in a “mirror image.” For example, the heart develops on the right side of the chest instead of on the left, while the liver grows on the left and the stomach and spleen on the right. Therefore, they learned, the cilia have an important function in fetal development.

Three of the affected patients at Hadassah suffered from transposition of organs.

The condition occurs in one out of 15,000 births, according to medical estimates, but Hadassah experts believe that it is actually more common, but many of the victims are not diagnosed.

So far, about 15 different genes responsible for the composition of the tiny hairs in the respiratory system have been discovered around the world. The damage to the delicate structure of the cilia can be observed through an electron microscope.

Kerem said that every cell in the respiratory system in the body is coated with hundreds of microscopic hairs that help protect it against infection.

The cilia are composed of hundreds of different proteins manufactured by many different genes, he continued, that cause the rigid structure to develop flexibility and the ability to move in coordination with nearby cilia.

These hairs also exist in the ears, brain and female reproductive system, including the fallopian tubes.

However, unlike the known genes responsible for cilia production, this is the first time that an active gene was found in the cytoplasm, a jelly-like substance that fills the cell and is contained inside the cell membrane.

The new gene, identified with help from the University of Washington in St. Louis, is not directly responsible for production of one of the components of cilia, but it has a more central function – supervising the construction of the cilia.

A cellular culture taken from the Hadassah patients showed a much-reduced expression in LRRC6 that caused irregular formation of the cilia and a much-reduced motility.

Kerem said that with the identification of the important gene, he and his colleagues hope to better understand the fetal development of organs and where they grow, as well as the action of the cilia.

As a result, they hope to diagnose patients much more quickly, so that maybe they can be helped before damage is done.

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