Abstract for presentation at 11th International Congress of Human Genetics

Clinical Phenotypes Associated with Mutations in TGFBR1 and TGFBR2 genes

  • Lesley Adès, Department of Clinical Genetics, The Children’s Hospital at Westmead, Westmead, Australia, Australia
  • Kate Sullivan, Department of Molecular Genetics, The Children’s Hospital at Westmead, Westmead, Australia, Australia
  • Katherine Holman, Department of Molecular Genetics, The Children’s Hospital at Westmead, Westmead, Australia, Australia
  • Dr Fiona Stewart, Department of Medical Genetics, Belfast City Hospital, Belfast, Ireland., Ireland
  • Dr Ian Walpole, Genetic Services of Western Australia, King Edward Memorial Hospital for Women, Subiaco, Western Australia., Australia
  • Prof Eric Haan, South Australian Clinical Genetics Services, Women’s and Children’s Hospital, North Adelaide, South Australia., Australia
  • Dr Maggie Brett, Department of Molecular Genetics, The Children’s Hospital at Westmead, Westmead, Australia, Australia
  • Dr Bruce Bennetts, Department of Molecular Genetics, The Children’s Hospital at Westmead, Westmead, Australia, Australia

    • Recent studies have highlighted the role of fibrillin-1 in the regulation of the TGF-ß signalling pathway. It has been shown that mutations in FBN1 may secondarily cause dysregulation of this pathway. Inversely, mutations in either TGFBR1 or TGFBR2 may also have deleterious effects on TGF-ß signalling; in some cases, this may also be reflected by abnormalities in fibrillin-1 protein expression within fibroblasts and possibly other cell lines.
    Mutations in TGFBR2 have been shown to cause a number of clinical phenotypes including Marfan syndrome (MFS2), a small percentage of cases of non-syndromal thoracic aortic dilatation and dissection (TAAD) and Loeys-Dietz syndrome (LDS). Mutations in TGFBR1 have been reported in association with Furlong syndrome (FS) and some cases of LDS. Whether or not mutations in TGFBR1 or TGFBR2 are responsible for any cases of Shprintzen-Goldberg syndrome (SGS) remains controversial and requires clarification.
    Previously, we have published the clinical and radiological features and disease progression in two unrelated individuals whose phenotype most closely resembled that of FS, and in whom an identical de novo TGFBR1 mutation, p.S241L, was found. We have continued to study an extensive patient cohort including those with Marfan syndrome in whom no FBN1 mutation or deletion has been identified, “atypical” Marfan syndrome patients, patients with extensive arterial aneurysms, Lujan-Fryns syndrome, TAAD, FS, LDS and SGS. Here, we present the clinical and molecular findings of this study to date.

    Conference Organiser - ICMS Pty Ltd