Sorted By Test Name - Mayo Medical Laboratories

TGFK2
89462
transforming growth factor beta receptor I (TGF beta R-I). TGF beta R-I is a 53 kilodalton protein that
belongs to the serine-threonine kinase family of cell surface receptors. This group of receptors regulates a
variety of cellular processes, including proliferation, differentiation, cell cycle arrest, apoptosis, and
formation of the extracellular matrix. Receptor activation occurs upon binding of TGF beta to
transforming growth factor beta receptor II (TGF beta R-II), which then recruits and phosphorylates TGF
beta R-I, propagating the signal to downstream transcription factors. Few genotype-phenotype
correlations exist for TGFBR1 mutations; indeed, identical mutations have been reported to cause
Marfan-like syndrome in some individuals, LDS in others, and FTAAD in others. Approximately 25% of
individuals with LDS have an affected parent; while 75% have a de novo mutation (de novo rate for
related phenotypes is not reported). TGFBR1 mutations can manifest with a range of phenotypes and
variable ages of onset both between families and amongst affected members of the same family. Thus,
TGFBR1-related disorders can be diagnostically challenging. Genetic testing for TGFBR1 mutations
allows for the confirmation of a suspected genetic disease. Confirmation of LDS or other
TGFBR1-associated genetic diseases allows for proper treatment and management of the disease.
Additionally, mutation confirmation can allow for preconception/prenatal and family counseling.
Useful For: Aiding in the diagnosis of TGFBR1-associated Loeys-Dietz syndrome, Marfan or
Marfan-like syndrome, familial thoracic aortic aneurysm and dissection syndrome, and
Shprintzen-Goldberg syndrome
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Loeys B, Chen J, Neptune E, et al: A syndrome of altered cardiovascular,
craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat
Genet 2005;37(3):275-281 2. Akutsu K, Morisaki H, Takeshita S, et al: Phenotypic heterogeneity of
Marfan-like connective tissue disorders associated with mutations in the transforming growth factor-beta
receptor genes. Circ J 2007;71(8):1305-1309 3. Drera B, Tadini G, Barlati S, Colombi M: Identification
of a novel TGFBR1 mutation in a Loeys-Dietz syndrome type II patient with vascular Ehlers-Danlos
syndrome phenotype. Clin Genet 2008;73(3):290-293 4. Singh K, Rommel K, Mishra A, et al: TGFBR1
and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. Hum
Mut 2006;27(8):770-777 5. Stheneur C, Collod-Beroud G, Faivre L, et al: Mutations and
genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz
syndrome and related disorders. Hum Mut Mutation in Brief 2008;(#1031)29:E284-295 online Epub
ahead of print).
TGFBR2 Gene, Known Mutation
Clinical Information: Mutations in the TGFBR2 gene have been implicated in a range of autosomal
dominant conditions with considerable phenotypic overlap. The genetic disease most commonly
associated with TGFBR2 mutations is Loeys-Dietz syndrome (LDS), which is characterized by cerebral,
thoracic, and abdominal arterial aneurysms and/or dissections, as well as skeletal anomalies (chest
abnormalities, scoliosis, joint laxity, arachnodactyly). LDS is divided into LDS type I and LDS type II
based on the phenotype, then further categorized depending on the causative gene. Both LDS type I and II
involve the cardiovascular and skeletal manifestations mentioned above. In addition, LDS type I involves
craniofacial manifestations including hypertelorism, bifid uvula/cleft palate, and craniosynostosis. LDS
type I caused by a TGFBR1 mutation is known as LDS1A, whereas LDS type I caused by a TGFBR2
mutation, is known as LDS1B. LDS type II has cutaneous manifestations including velvety and
translucent skin, easy bruising, widened and atrophic scars, and uterine rupture. LDS type II caused by a
TGFBR1 mutation is known as LDS2A, whereas LDS type II caused by a TGFBR2 mutation is known as
LDS2B. Identical mutations can lead to LDS type I or type II, supporting the belief that both types are
part of a clinical continuum. Mutations in the TGFBR2 gene have also been identified in conditions with
phenotypic overlap with LDS. Marfan syndrome (MFS) is a systemic connective tissue disorder involving
the ocular, skeletal, and cardiovascular systems. MFS is most often associated with mutations in the
FBN1 gene; however some individuals who meet or nearly meet the clinical diagnostic criteria for MFS
have been shown to have mutations in TGFBR2. Familial thoracic aortic aneurysm and dissection
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