Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome.
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 inTGFBR2and 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 ofTGFBR2was 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.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Michael T
MT
Zimmermann
Laboratory of Epigenetics and Chromatin Dynamics, Departments of Biochemistry and Molecular Biology, Biophysics, and Medicine, Mayo Clinic, Rochester, MN, USA.
Raul A
RA
Urrutia
Department of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Jacksonville, FL, USA.
Patrick R
PR
Blackburn
Center for Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Margot A
MA
Cousin
Center for Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Nicole J
NJ
Boczek
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Center for Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Eric W
EW
Klee
Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Colleen
C
Macmurdo
Department of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Jacksonville, FL, USA; Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Paldeep S
0000-0002-8515-744X
PS
Atwal