Discovery of the genetic basis of two diseases

In a first article, Loeys et al describe a new aortic aneurysm syndrome characterized by the main triad of hypertelorism,
bifid uvula and/or cleft palate and aortic aneurysms with arterial tortuosity. This new entity also presents with alterations
of the skeletal, craniofacial, neurocognitve development. Importantly, the nature of the aortic aneurysms seems very
aggressive and aneurysms occur throughout the arterial tree. In a collaboration between Johns Hopkins University in Baltimore
and Ghent University in Belgium, it was demonstrated that this disease is caused by mutations in either of the genes encoding
for transforming growth factor receptor 1 or 2 (TGFBR1 or 2).


In a second article, homozygosity mapping of a Senior-Loken family evaluated at the Ghent University led to the idenfication
of a region on the long arm of chromosome 3. Researchers of the Ann Harbor University in Michigan went on to clone a new
gene, nephrocystin-5, a ciliary IQ domain protein. Senior-Loken syndrome is characterized by the association of
nephronophtisis and retinitis pigmentosa. These studies emphasize the central role of ciliary dysfunction in the pathogenesis
of Senior-Loken syndrome.


Peer reviewed publication and references

Nature Genetics, 2005, 37: 275-281.

Nature Genetics, 2005, 37: 282-288.


A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or
TGFBR2.

Loeys B., Chen J., Neptune E.R., Judge D.P., Podowski M., Holm T., Meyers J., Leitch C.C., Katsanis N., Sharifi N., Xu F.L.,
Myers L.A., De Backer J., Hellemans J., Chen Y., Davis E.C., Webb C.L., Kress W., Spevak P.J., Coucke P., Rifkin D.B., De
Paepe A., Dietz H.C.

Nature Genetics, 2005, 37: 275-281.


Nephrocystin-5, a ciliary IQ domain protein is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin.

Otto E.A., Loeys B., Kahnna H., Hellemans J., Sudbrak R., Fan S., Muerb U., O'Toole J.F., Helou J., Attanasio M., Utsch B.,
Sayer J.A., Lillo C., Jimeno D., Coucke P., De Paepe A., Reinhardt R., Klages S., Tsuda M., Kawakami I., Kusakabe T., Omran
H., Imm A., Tippens M., Raymond P.A., Hill J., Beales P., He S., Kispert A., Margolis B., Williams D.S., Swaroop A.,
Hildebrandt F.

Nature Genetics, 2005, 37: 282-288.


GHENT UNIVERSITY

(The largest and oldest public university in Belgium)

Het Pand,

Onderbergen 1,

B-9000 Gent,

rug.ac.be

SOURCE: alphagalileo