Sorted By Test Name - Mayo Medical Laboratories

TGF1
89459
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: Genetic testing of individuals at risk for a known TGFBR1 mutation
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
Mutat 2006 Aug;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 Mutat 2008 Nov;29(11):E284-295
TGFBR1, Full Gene Sequence
Clinical Information: Mutations in the TGFBR1 gene have been implicated in a range of autosomal
dominant conditions with a considerable degree of phenotypic overlap. The genetic disease most
commonly associated with TGFBR1 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 can also be caused by mutations in the
TGFBR2 gene. LDS is divided into LDS type I and LDS type II based on 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 TGFBR1 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 the TGFBR1 gene. Some individuals with mutations in TGFBR1 present with features
similar to those seen in vascular type Ehlers-Danlos syndrome (EDS type IV), such as visceral rupture,
easy bruising, wide and atrophic scars, joint laxity, translucent skin, velvety skin, or both. In addition,
familial thoracic aortic aneurysm and dissection (FTAAD), which involves cardiovascular manifestations
only, has been associated with mutations in TGFBR1. Mutations in TGFBR1 may also be observed in
Shprintzen Goldberg syndrome (SGS), which is characterized by craniosynostosis, distinctive craniofacial
features, skeletal changes, neurologic abnormalities, mental retardation, and brain anomalies among other
features. The TGFBR1 gene, which contains 9 exons and is located on chromosome 9q22, encodes the
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