Loeys-Dietz syndrome type 4, caused by chromothripsis, involving the TGFB2 gene.
The TGF-β signaling pathway controls cellular proliferation, growth and differentiation and regulates several functions of the connective tissue. Disruption of genes coding for components of the TGF-β signaling pathway or its interactors, such as fibrillin-1, has been shown to cause several human pathologies. Large deletions and non-sense mutations in TGFB2 gene have been recently described in patients with aortic aneurysm, scoliosis, arachnodactyly, chest deformities, joint hyper-flexibility, and mild intellectual disability; this condition has been called Loeys-Dietz syndrome, type 4. In this paper we describe an 18-year-old girl with borderline mental impairment, seizures, retinal degeneration, short stature, congenital hip dysplasia, severe and worsening joint hypermobility, scoliosis, progressive deformation of the long bones, aortic dilatation and platelet disorder. Molecular study of DNA by Array-CGH demonstrated four de novo microdeletions: TGFB2 is among the genes deleted and we consider it the obvious candidate for the clinical phenotype. The multiple chromosomal rearrangements detected in the current patient can be ascribed to an event of constitutional chromothripsis.
Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy. Electronic address: Sibusiso.fontana@gmail.com.
Paolo
P
Fontana
Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
Rita
R
Genesio
Department of Translational Medical Sciences, Division of Pediatrics, Federico II University, Naples, Italy.
Alberto
A
Casertano
Department of Translational Medical Sciences, Division of Pediatrics, Federico II University, Naples, Italy.
Gerarda
G
Cappuccio
Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
Angela
A
Mormile
Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
Lucio
L
Nitsch
Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
Achille
A
Iolascon
Department of Translational Medical Sciences, Division of Pediatrics, Federico II University, Naples, Italy.
Generoso
G
Andria
Department of Translational Medical Sciences, Division of Pediatrics, Federico II University, Naples, Italy.
Daniela
D
Melis
D000293:Adolescent; D019457:Chromosome Breakage; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000175:diagnosis / Q000235:genetics*; D053781:Transforming Growth Factor beta2 / Q000235:genetics*
C509041:TGFB2 protein, human; D053781:Transforming Growth Factor beta2
Array-CGH; Chromothripsis; Joint hypermobility; RUNX1; TGFB2