Faculty Collaboration Database

Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome. Case Rep Genet 2017;2017:7263780

Date

02/07/2017

Pubmed ID

28163941

Pubmed Central ID

PMC5253504

DOI

10.1155/2017/7263780

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.

Author List

Zimmermann MT, Urrutia RA, Blackburn PR, Cousin MA, Boczek NJ, Klee EW, Macmurdo C, Atwal PS

Authors

Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
Michael T. Zimmermann PhD Director, Assistant Professor in the Clinical and Translational Science Institute department at Medical College of Wisconsin