Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice

Nature ◽  
2001 ◽  
Vol 410 (6824) ◽  
pp. 97-101 ◽  
Author(s):  
Elizabeth A. Lindsay ◽  
Francesca Vitelli ◽  
Hong Su ◽  
Masae Morishima ◽  
Tuong Huynh ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Digeorge Syndrome ◽  
Tbx1 Haploinsufficiency

A genetic link between Tbx1 and fibroblast growth factor signaling

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4605-4611 ◽  
Author(s):  
Francesca Vitelli ◽  
Ilaria Taddei ◽  
Masae Morishima ◽  
Erik N. Meyers ◽  
Elizabeth A. Lindsay ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Expression Patterns ◽  
Pharyngeal Arch ◽  
Growth Factor Signaling ◽  
Expression Domain ◽  
Primary Defect ◽  
Genetic Link ◽  
Pharyngeal Endoderm ◽  
Pharyngeal Arch Arteries ◽  
Tbx1 Haploinsufficiency

Tbx1 haploinsufficiency causes aortic arch abnormalities in mice because of early growth and remodeling defects of the fourth pharyngeal arch arteries. The function of Tbx1 in the development of these arteries is probably cell non-autonomous, as the gene is not expressed in structural components of the artery but in the surrounding pharyngeal endoderm. We hypothesized that Tbx1 may trigger signals from the pharyngeal endoderm directed to the underlying mesenchyme. We show that the expression patterns of Fgf8 and Fgf10, which partially overlap with Tbx1 expression pattern, are altered in Tbx1–/– mutants. In particular, Fgf8 expression is abolished in the pharyngeal endoderm. To understand the significance of this finding for the pathogenesis of the mutant Tbx1 phenotype, we crossed Tbx1 and Fgf8 mutants. Double heterozygous Tbx1+/–;Fgf8+/– mutants present with a significantly higher penetrance of aortic arch artery defects than do Tbx1+/–;Fgf8+/+ mutants, while Tbx1+/+;Fgf8+/– animals are normal. We found that Fgf8 mutation increases the severity of the primary defect caused by Tbx1 haploinsufficiency, i.e. early hypoplasia of the fourth pharyngeal arch arteries, consistent with the time and location of the shared expression domain of the two genes. Hence, Tbx1 and Fgf8 interact genetically in the development of the aortic arch. Our data provide the first evidence of a genetic link between Tbx1 and FGF signaling, and the first example of a modifier of the Tbx1 haploinsufficiency phenotype. We speculate that the FGF8 locus might affect the penetrance of cardiovascular defects in individuals with chromosome 22q11 deletions involving TBX1.

scholarly journals Interrupted right aortic arch in DiGeorge syndrome.

Heart ◽  
1987 ◽  
Vol 58 (3) ◽  
pp. 274-278 ◽  
Author(s):  
P Moerman ◽  
M Dumoulin ◽  
J Lauweryns ◽  
L G Van der Hauwaert
Keyword(s):  
Aortic Arch ◽  
Digeorge Syndrome ◽  
Right Aortic Arch

scholarly journals A phenotypic rescue approach identifies lineage regionalization defects in a mouse model of DiGeorge syndrome

2021 ◽  
Author(s):  
Gabriella Lania ◽  
Monica Franzese ◽  
Adachi Noritaka ◽  
Marchesa Bilio ◽  
Annalaura Russo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vitamin B12 ◽  
Aortic Arch ◽  
Digeorge Syndrome ◽  
Molecular Level ◽  
Cellular Distribution ◽  
Cell Distribution ◽  
Pharyngeal Apparatus ◽  
Phenotypic Rescue

ABSTRACTTBX1 is a key regulator of pharyngeal apparatus (PhAp) development. Vitamin B12 treatment partially rescues aortic arch patterning defects of Tbx1+/- embryos. Here we show that it also improves cardiac outflow tract septation and branchiomeric muscle anomalies of Tbx1 hypomorphic mutants. At molecular level, the in vivo vB12 treatment let us to identify genes that were dysregulated by Tbx1 haploinsufficiency and rescued by treatment. We found that SLUG, encoded by the rescued gene Snai2, identified a population of mesodermal cells that was partially overlapping with but distinct from ISL1+ and TBX1+ populations. In addition, SLUG+ cells were mislocalized and had a greater tendency to aggregate in Tbx1+/- and Tbx1-/- embryos and vB12 treatment restore cellular distribution. Adjacent neural crest-derived mesenchymal cells, which do not express TBX1, were also affected, showing enhanced segregation from cardiopharyngeal mesodermal cells. We propose that TBX1 regulates cell distribution in core mesoderm and the arrangement of multiple lineages within the PhAp.

Adult Aortotracheal Fistula as Sequela of Double Aortic Arch Repair in Infancy: A Case Report

2020 ◽  
Vol 129 (7) ◽  
pp. 649-652
Author(s):  
Andrew B. Rees ◽  
Jennifer P. Rodney ◽  
Mark R. Gilbert ◽  
Clayton A. Kaiser ◽  
Alexander H. Gelbard
Keyword(s):  
Aortic Arch ◽  
Digeorge Syndrome ◽  
Surgical Repair ◽  
Surgical Intervention ◽  
Vascular Ring ◽  
Clinical History ◽  
Double Aortic Arch ◽  
Aortic Arch Repair ◽  
Early Surgical Intervention

Introduction: Double aortic arch is a rare congenital malformation of the aortic arch that most frequently presents in childhood. Early surgical intervention typically yields excellent outcomes. Objectives: To describe aortotracheal fistula as a rare, yet serious complication of vascular ring and subsequent aortic aneurysm in an adult patient. Methods: Clinical history, as well as radiographic and endoscopic imaging were obtained to describe the development, diagnosis, and clinical course of this patient’s aortotracheal fistula. Additionally, follow up data was obtained to document the healing of this fistula after surgical repair. Results: We describe a case of a 46-year-old male with DiGeorge Syndrome and a double aortic arch, repaired in childhood, which developed into an aortotracheal fistula after tracheostomy placement as an adult. Conclusions: This case demonstrates that dangerous complications of a double aortic arch can persist into adulthood, even after surgical repair in infancy. Each patient’s unique anatomy must be considered when thinking about airway management and prevention of complications of this rare congenital anomaly.

Interruption of the aortic arch at the isthmus with DiGeorge syndrome and 22q11.2 deletion

1999 ◽  
Vol 9 (5) ◽  
pp. 516-518 ◽  
Author(s):  
Kazuhiro Takahashi ◽  
Takashi Kuwahara ◽  
Masayoshi Nagatsu
Keyword(s):  
Aortic Arch ◽  
Digeorge Syndrome ◽  
Septal Defect ◽  
Left Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Interrupted Aortic Arch ◽  
Left Ventricular ◽  
22Q11.2 Deletion ◽  
Left Ventricular Outflow

AbstractA 6-day-old male with interruption of the aortic arch at the isthmus (type A) had the typical phenotype of DiGeorge syndrome. There was also a doubly committed juxta-arterial ventricular septal defect and an unobstructed left ventricular outflow tract. Hypoplasia of the thymus was confirmed during a modified Blalock-Park operation. He had persistent hypocalcemia, and was susceptible to infection. He was subsequently revealed by the use of fluorescence in situ hybridization analysis to have 22q11.2 deletion. Interruption of the aortic arch at the isthmus is presumed to reflect abnormal fetal hemodynamics, and is considered a distinct pathogenetic entity from interruption between the left common carotid and subclavian arteries, the latter being the variant more frequently associated with DiGeorge syndrome. In our case, the 22q11.2 deletion likely played a major role in the etiology of the interrupted aortic arch.

scholarly journals Truncus arteriosus associated with double aortic arch in a patient with DiGeorge syndrome: A rare case report

2019 ◽  
Vol 12 (2) ◽  
pp. 185 ◽  
Author(s):  
Azin Ghamari ◽  
EhsanAghaei Moghadam ◽  
MohamadReza Mirzaaghayan ◽  
Aliakbar Zeinaloo ◽  
Ali Mohebbi
Keyword(s):  
Case Report ◽  
Aortic Arch ◽  
Digeorge Syndrome ◽  
Rare Case ◽  
Double Aortic Arch ◽  
Truncus Arteriosus ◽  
Rare Case Report
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