TBX2 gene duplication associated with complex heart defect and skeletal malformations.
We report on a patient with mild mental retardation, prenatal onset growth retardation, cerebellar hypoplasia, and complex heart defect including: interventricular septal defect, patent foramen ovale, aortic coarctation, tricuspid valve insufficiency, mitral valve stenosis, and minor skeletal anomalies with hypo-aplasia of the distal phalanges. A SNP-array analysis detected a de novo duplication of 17q23.2, encompassing the TBX2 gene. Animal models argue for a key role of Tbx2 during cardiac and limb development. Accordingly, we hypothesize that the heart malformation and mild digital anomalies found in this patient could be related to TBX2 gene overexpression, suggesting parallel consequences of TBX2 gene dosage imbalances in animals and in humans.
Radio
Francesca Clementina
FC
Casa Sollievo della Sofferenza Hospital, IRCSS, San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy.
Bernardini
Laura
L
Loddo
Sara
S
Bottillo
Irene
I
Novelli
Antonio
A
Mingarelli
Rita
R
Dallapiccola
Bruno
B
D000328:Adult; D001842:Bone and Bones / Q000002:abnormalities* / Q000473:pathology; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D005260:Female; D020440:Gene Duplication; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics*
D012333:RNA, Messenger; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins