A Novel Mutation of TGFB2 Gene Responsible of Loeys-Dietz 4 Syndrome

Erika Di Zazzo,1,2 Autilia Tommasina Buonagura,3,4 Veronica Palladino,5 Michele Pinelli,3,4 Silvio Garofalo1,2 1Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy; 2Unit of Laboratory Medicine, Cardarelli Hospital, Campobasso, Italy; 3Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy; 4Unit of Medical Genetics, University Hospital Federico II, Naples, Italy; 5Unit of Transfusion Medicine, Cardarelli Hospital, Campobasso, ItalyCorrespondence: Erika Di Zazzo, Email [email protected]: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by vascular and skeletal abnormalities. LDS, classified into six subtypes (LDS1– 6), is caused by mutations in the genes encoding proteins involved in the transforming growth factor-beta (TGF-β) signaling pathway. LDS4 is the mild form of the LDS spectrum, considering that aneurysms are observed in the fourth decade and the disease progression is slower than the other forms.Case Presentation: We reported the case of a novel TGFB2 variant c.280_298del p.(Ser94Profs*7), NM_001135599.2 responsible of LDS4 in a family with sudden death and vascular lesions.Conclusion: The pedigree analysis highlighted the high clinical variability of LDS signs even within the same family. In addition, TGFB2 mutations which do not always lead to vascular phenotype and skeletal signs can be prevalent. We emphasize the relevance of genetic counseling and molecular analysis to identify genetic diseases subtending sudden deaths and to distinguishing heritable connective tissue disorders with phenotypic overlap. Genetic testing can be used to guide clinical management and provide valuable prognostic information.Keywords: Loeys-Dietz syndrome, TGF-β, next generation sequencing