Mutations in PITX2 may contribute to cases of omphalocele and VATER-like syndromes.

Abstract

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.

• Authors: L A Katz, R E Schultz, E V Semina, C P Torfs, K N Krahn, J C Murray
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 130A Issue 3 Pg. 277-83 (Oct 15 2004) ISSN: 1552-4825 [Print] United States
• PMID: 15378534 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Homeodomain Proteins
• Transcription Factors
• homeobox protein PITX2

Topics

• Abnormalities, Multiple (genetics, pathology)
• Animals
• Base Sequence
• Conserved Sequence (genetics)
• DNA Mutational Analysis
• Evolution, Molecular
• Hernia, Umbilical (genetics, pathology)
• Homeodomain Proteins (genetics)
• Humans
• Infant
• Molecular Sequence Data
• Mutation
• Sequence Alignment
• Sequence Homology, Nucleic Acid
• Syndrome
• Transcription Factors (genetics)