Marfan Syndrome: Growth Factor Mutations Linked

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Growth Factor Mutations Linked to Marfan Syndrome

NEW YORK (Reuters Health) Jul 27 - Mutations in the gene encoding

transforming growth factor-beta receptor 2 (TGFBR2) appear to be involved in

some cases

of Marfan syndrome, according to a recent report.

Dr. Naomichi Matsumoto and associates identified the abnormality in a

Japanese patient with Marfan syndrome lacking abnormalities in the fibrillin

(FBN1) gene, a previously recognized defect in Marfan syndrome. They

describe their findings in Nature Genetics published online July 4th.

Dr. Matsumoto, at Yokahama City University Graduate School of Medicine in

Japan, and associates analyzed TGFBR2 in a large French family affected by

Marfan

syndrome. There were abnormalities in TGFBR2 of the 12 affected members and

in 13 of 14 members with an ambiguous status. The mutation was absent in 32

healthy siblings and 16 unrelated spouses.

They next studied 9 unrelated French individuals and 10 unrelated Japanese

individuals with Marfan syndrome, none of whom carried abnormalities in FBN1

gene. In this group they identified three additional missense mutations in

TGFBR2.

Further investigation revealed that the mutations decreased TGF-beta

signaling. The authors note that these cytokines regulate numerous cellular

processes,

such as proliferation, differentiation and apoptosis, and that TGF-beta is a

putative tumor-suppressor gene implicated in several types of cancer.

In the current report, they traced the identified abnormalities back to

suppression of an extra cellular matrix protein, plasminogen activator

inhibitor

type 1 (PAI-1). The disorder manifested as prominent aortic, skeletal and

integument anomalies, along with ocular and pulmonary anomalies.

Dr. Matsumoto's team points out that some of the families studied lacked

abnormalities in FBN1 and in TGFBR2. " This observation could indicate that

there

is a higher degree of genetic heterogeneity for Marfan syndrome. "

Nat Genet 2004.

Reuters Health Information 2004. © 2004 Reuters Ltd.

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http://www.medscape.com/viewarticle/484298