Journal article
Mutations in PITX2 may contribute to cases of omphalocele and VATER-like syndromes
American journal of medical genetics. Part A, Vol.130A(3), pp.277-283
10/15/2004
DOI: 10.1002/ajmg.a.30329
PMID: 15378534
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.
Details
- Title: Subtitle
- Mutations in PITX2 may contribute to cases of omphalocele and VATER-like syndromes
- Creators
- L A Katz - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USAR E SchultzE V SeminaC P TorfsK N KrahnJ C Murray
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.130A(3), pp.277-283
- DOI
- 10.1002/ajmg.a.30329
- PMID
- 15378534
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Publisher
- United States
- Grant note
- ES10876 / NIEHS NIH HHS DE08559 / NIDCR NIH HHS EY12384 / NEI NIH HHS T32 GM007337 / NIGMS NIH HHS
- Language
- English
- Date published
- 10/15/2004
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025420802771
Metrics
19 Record Views