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 in TGFBR2 and phenotype consistent with classic LDS. The prob...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Case Reports in Genetics |
| Online Access: | http://dx.doi.org/10.1155/2017/7263780 |
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| author | Michael T. Zimmermann Raul A. Urrutia Patrick R. Blackburn Margot A. Cousin Nicole J. Boczek Eric W. Klee Colleen Macmurdo Paldeep S. Atwal |
| author_facet | Michael T. Zimmermann Raul A. Urrutia Patrick R. Blackburn Margot A. Cousin Nicole J. Boczek Eric W. Klee Colleen Macmurdo Paldeep S. Atwal |
| author_sort | Michael T. Zimmermann |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cb1a95c6c1b749a89383dc7dfaf49d3c |
| institution | Kabale University |
| issn | 2090-6544 2090-6552 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Genetics |
| spelling | doaj-art-cb1a95c6c1b749a89383dc7dfaf49d3c2025-02-03T06:07:15ZengWileyCase Reports in Genetics2090-65442090-65522017-01-01201710.1155/2017/72637807263780Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz SyndromeMichael T. Zimmermann0Raul A. Urrutia1Patrick R. Blackburn2Margot A. Cousin3Nicole J. Boczek4Eric W. Klee5Colleen Macmurdo6Paldeep S. Atwal7Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USALaboratory of Epigenetics and Chromatin Dynamics, Departments of Biochemistry and Molecular Biology, Biophysics, and Medicine, Mayo Clinic, Rochester, MN, USADepartment of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Jacksonville, FL, USACenter for Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USACenter for Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USADivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USADivision of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USADepartment of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Jacksonville, FL, USALoeys-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.http://dx.doi.org/10.1155/2017/7263780 |
| spellingShingle | Michael T. Zimmermann Raul A. Urrutia Patrick R. Blackburn Margot A. Cousin Nicole J. Boczek Eric W. Klee Colleen Macmurdo Paldeep S. Atwal Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome Case Reports in Genetics |
| title | Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome |
| title_full | Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome |
| title_fullStr | Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome |
| title_full_unstemmed | Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome |
| title_short | Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome |
| title_sort | novel pathogenic variant in tgfbr2 confirmed by molecular modeling is a rare cause of loeys dietz syndrome |
| url | http://dx.doi.org/10.1155/2017/7263780 |
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