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Mutations in PITX2 may contribute to cases of omphalocele and VATER-like syndromes. Am J Med Genet A 2004 Oct 15;130A(3):277-83



Pubmed ID




Scopus ID

2-s2.0-4744372136   19 Citations


Omphalocele is a congenital anomaly with substantial morbidity. Rieger syndrome, an autosomal dominant disorder, is characterized by craniofacial abnormalities and abdominal wall defects. PITX2 mutations are etiologic in >40% of cases of Rieger syndrome. We demonstrate that the birth prevalence of omphalocele is significantly higher in Rieger syndrome than in the general population, with omphaloceles found in 0.03% in the Iowa newborn population and 4.3% of patients with Rieger syndrome. Our objective was to screen coding and conserved non-coding regions of PITX2 for mutations in 209 patients with omphalocele. We identified remarkable evolutionarily conserved regions by comparing the 3'UTR of Pitx2 in 13 vertebrate and 3 invertebrate species. No mutations changing the amino acid sequence were found within the omphalocele population. In one case of omphalocele with VATER-like additional anomalies, a three nucleotide deletion was found in the 3'UTR. This deletion was not seen in 1,186 controls. Also in the 3'UTR, we identified a single nucleotide polymorphism at a highly conserved residue. Our findings suggest additional studies of PITX2 conserved regions will be valuable. We also screened the omphalocele cases for mutations in exon 5 of the gene FLNA. Mutations in FLNA have been shown to cause a broad range of congenital malformations, including otopalatodigital syndrome type 2 in which a missense mutation occurring in exon 5 of FLNA results in omphalocele as part of the phenotype. We did not find any mutations in exon 5 of FLNA in 179 omphalocele cases studied.

Author List

Katz LA, Schultz RE, Semina EV, Torfs CP, Krahn KN, Murray JC


Elena V. Semina PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Abnormalities, Multiple
Base Sequence
Conserved Sequence
DNA Mutational Analysis
Evolution, Molecular
Hernia, Umbilical
Homeodomain Proteins
Molecular Sequence Data
Sequence Alignment
Sequence Homology, Nucleic Acid
Transcription Factors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a