A Nonsense SMAD3 Mutation in a Girl with Familial Thoracic Aortic Aneurysm and Dissection without Joint Abnormality.

INTRODUCTION

Thoracic aortic aneurysms and dissections (TAAD) are rare in children and often associated with underlying genetic disorders accompanied with other systemic manifestations, including connective or osteo-articular tissue diseases.

CASE PRESENTATION: We report the case of a 10-year-old girl with a novel nonsense SMAD3 mutation, p.Glu102X, who presented with familial TAAD without any signs of osteoarthritis. Histological analysis of aorta fragments from the patient with TAAD obtained during surgery revealed elastin degradation and inflammatory infiltration of T cells with dense CD31 + microvessels, which is consistent with previous findings. Interestingly, the family members with the SMAD3 mutation developed IgA nephropathy.

CONCLUSION

Because the TGF-β/Smad signalling pathway plays an important role in the primary pathogenesis of IgA nephropathy and TAAD, we presume that IgA nephropathy could be a novel clinical phenotype of SMAD3 deficiency. Further accumulation of genetically proven cases with SMAD3 deficiency is needed to more accurately characterize phenotypic variability and elucidate a wide spectrum of TGF-β-associated disorders.