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
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
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
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
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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