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https://hdl.handle.net/2440/35751
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Type: | Journal article |
Title: | FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited |
Author: | Ades, L. Sullivan, K. Biggin, A. Haan, E. Brett, M. Holman, K. Dixon, J. Robertson, S. Holmes, A. Rogers, J. Bennetts, B. |
Citation: | American Journal of Medical Genetics Part A, 2006; 140A(10):1047-1058 |
Publisher: | Wiley-Liss |
Issue Date: | 2006 |
ISSN: | 1552-4825 1552-4833 |
Statement of Responsibility: | L.C. Adès, K. Sullivan, A. Biggin, E.A. Haan, M. Brett, K.J. Holman, J. Dixon, S. Robertson, A.D. Holmes, J. Rogers, B. Bennetts |
Abstract: | The recent identification of TGFBR2 mutations in Marfan syndrome II (MFSII) [Mizuguchi et al. (2004); Nat Genet 36:855-860] and of TGFBR1 and TGFBR2 mutations in Loeys-Dietz aortic aneurysm syndrome (LDS) [Loeys et al. (2005); Nat Genet 37:275-281] [OMIM 609192] has provided direct evidence of abnormal signaling in transforming growth factors beta (TGF-beta) in the pathogenesis of Marfan syndrome (MFS). In light of this, we describe the phenotypes and genotypes of five individuals. Patient 1 had MFS and abnormal cranial dura. Patient 2 had severe early onset MFS and an abnormal skull. Patients 3 and 4 had probable Furlong syndrome (FS). Patient 5 had marfanoid (MD) features, mental retardation (MR), and a deletion of chromosome 15q21.1q21.3. All patients had a condition within the MFS, MD-craniosynostosis (CS) or MD-MR spectrum. The names of these entities may become redundant, and instead, come to be considered within the spectrum of TGF-beta signaling pathway disorders. Two recurrent heterozygous FBN1 mutations were found in Patients 1 and 2, and an identical novel heterozygous de novo TGFBR1 mutation was found in Patients 3 and 4, in whom altered fibrillin-1 processing was demonstrated previously [Milewicz et al. (2000); Am J Hum Genet 67:279]. A heterozygous FBN1 deletion was found in Patient 5. These findings support the notion that perturbation of extracellular matrix homeostasis and/or remodeling caused by abnormal TGF-beta signaling is the core pathogenetic mechanism in MFS and related entities including the MD-CS syndromes. |
Keywords: | Humans Craniosynostoses Marfan Syndrome Abnormalities, Multiple Chromosome Deletion Syndrome Microfilament Proteins Activin Receptors, Type I Receptors, Transforming Growth Factor beta DNA Mutational Analysis Mutation Adolescent Adult Child Infant Male Intellectual Disability Fibrillin-1 Fibrillins Receptor, Transforming Growth Factor-beta Type I Protein Serine-Threonine Kinases |
Description: | Article first published online: 4 APR 2006 |
Rights: | Copyright © 2006 Wiley-Liss, Inc. |
DOI: | 10.1002/ajmg.a.31202 |
Published version: | http://dx.doi.org/10.1002/ajmg.a.31202 |
Appears in Collections: | Aurora harvest 6 Paediatrics publications |
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