New Hereditary Lymphedema Gene

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New Hereditary Lymphedema Gene

Postby patoco » Sat May 29, 2010 9:04 am

Researchers discover gene mutation linked to lymphatic dysfunction

May 27, 2010

Preface from PDF article ****Lymphedema is the clinical manifestation of defects
in lymphatic structure or function. Mutations identified in genes regulating
lymphatic development result in inherited lymphedema. No mutations have yet been
identified in genes mediating lymphatic function that result in inherited
lymphedema. Survey microarray studies comparing lymphatic and blood endothelial
cells identified expression of several connexins in lymphatic endothelial cells.
Additionally, gap junctions are implicated in maintaining lymphatic flow.

By sequencing GJA1, GJA4, and GJC2 in a group of families with dominantly
inherited lymphedema, we identified six probands with
unique missense mutations in GJC2 (encoding connexin [Cx] 47). Two larger
families cosegregate lymphedema and GJC2 mutation
(LOD score ¼ 6.5). We hypothesize that missense mutations in GJC2 alter gap
junction function and disrupt lymphatic flow. Until
now, GJC2 mutations were only thought to cause dysmyelination, with primary
expression of Cx47 limited to the central nervous
system. The identification of GJC2 mutations as a cause of primary lymphedema
raises the possibility of novel gap-junction-modifying
agents as potential therapy for some forms of lymphedema.*****

A genetic mutation for inherited lymphedema associated with lymphatic function
has been discovered that could help create new treatments for the condition, say
researchers at the University of Pittsburgh Graduate School of Public Health.
Their findings are reported in the June issue of the American Journal of Human

Lymphedema, the swelling of body tissues caused by an accumulation of fluid in a
blocked or damaged lymphatic system, affects more than 120 million people
worldwide. The most common treatments are a combination of massage, compression
garments or bandaging.

"Lymphedema was first described hundreds of years ago, and yet it remains a very
poorly understood disease," said David N. Finegold, M.D., co-principal
investigator of the study and professor of human genetics, University of
Pittsburgh Graduate School of Public Health. "Unfortunately, there is no drug
available to cure or even treat it. Most people with inherited lymphedema suffer
their entire lives with treatments that address symptom relief only."

The study is based on the University of Pittsburgh Lymphedema Family Study,
which began collecting data from affected families in 1995 to learn more about
the risk factors and causes of inherited, or primary, lymphedema.

Previous research has helped identify six genes linked to the development of
lymphedema, but until now researchers had no insight into the genetic factors
responsible for lymphatic vascular abnormalities.

In their study, Dr. Finegold and colleagues sequenced three genes expressed in
families with primary lymphedema. Mutations in one of these genes, GJC2, was
found in primary lymphedema families and are likely to impair the ability of
cells to push fluid throughout the lymphatic system by interrupting their

Without proper signaling, cell contraction necessary for the movement of fluid
did not occur, leading to its accumulation in soft body tissues.

"These results are significant because they give us insight into the cell
mechanics that may underlie this condition," said Dr. Finegold. "With further
research, we may be able to target this gene with drugs and improve its

More information PDF article: ... 7_lofnq2.p\
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