Novel pathogenic variant in TGFBR2 confirmed by molecular modeling is a rare cause of Loeys-Dietz syndrome

Zimmermann, M. T., Urrutia, R. A., Blackburn, P. R., Cousin, M. A., Boczek, N. J., Klee, E. W., Macmurdo, C. and Atwal, P. S. (2017) Novel pathogenic variant in TGFBR2 confirmed by molecular modeling is a rare cause of Loeys-Dietz syndrome. Case Reports in Genetics, 2017, 7263780. (doi: 10.1155/2017/7263780) (PMID:28163941) (PMCID:PMC5253504)

Abstract

Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular findings of aneurysm and/or dissection of cerebral, thoracic, or abdominal arteries and skeletal findings. We report a case of a novel pathogenic variant in TGFBR2 and phenotype consistent with classic LDS. The proband was a 10-year-old presenting to the genetics clinic with an enlarged aortic root (Z-scores 5-6), pectus excavatum, and congenital contractures of the right 2nd and 3rd digit. Molecular testing of TGFBR2 was sent to a commercial laboratory and demonstrated a novel, likely pathogenic, variant in exon 4, c.1061T>C, p.(L354P). Molecular modeling reveals alteration of local protein structure as a result of this pathogenic variant. This pathogenic variant has not been previously reported in LDS and thus expands the pathogenic variant spectrum of this condition.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Atwal, Dr Paldeep
• Authors: Zimmermann, M. T., Urrutia, R. A., Blackburn, P. R., Cousin, M. A., Boczek, N. J., Klee, E. W., Macmurdo, C., and Atwal, P. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Case Reports in Genetics
• Publisher: Hindawi
• ISSN: 2090-6544
• ISSN (Online): 2090-6552
• Published Online: 09 January 2017
• Copyright Holders: Copyright © 2017 Michael T. Zimmermann et al.
• First Published: First published in Case Reports in Genetics 2017: 7263780
• Publisher Policy: Reproduced under a Creative Commons License