Exclusion of PITX2 mutations as a major cause of CHARGE association

Donna M. Martin, Frank J. Probst, Sharon E. Fox, Lisa A. Schimmenti, Elena V. Semina, Margaret A. Hefner, John W. Belmont, Sally A. Camper

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19 Scopus citations


CHARGE is a nonrandom association of ocular coloboma, congenital heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear anomalies including deafness. The cause of CHARGE remains unknown; however, there is considerable evidence of an underlying genetic basis, as discussed by Tellier et al. [1996: Clin Genet 50:548-550; 1998: Am J Med Genet 76:402-409] and by Martin et al. [2001: Am J Med Genet 99:115-119]. Based on the ocular, cardiac, and craniofacial expression pattern of Pitx2, a homeodomain transcription factor, and the pleiotropic effects of loss of PITX2 function in both mouse and human, we hypothesized that PITX2 mutations may contribute to the multiple phenotypic anomalies present in CHARGE individuals. By direct sequencing of DNA from 29 individuals with CHARGE, we did not identify any mutations in PITX2. We did, however, identify two PITX2 sequence polymorphisms. Large deletions of PITX2 were excluded in most patients by heterozygosity in at least one of several polymorphic markers near the PITX2 locus. Together, these data indicate that PITX2 mutations are unlikely to be a major contributing cause of the multiple anomalies present in individuals with CHARGE.

Original languageEnglish (US)
Pages (from-to)27-30
Number of pages4
JournalAmerican Journal of Medical Genetics
Issue number1
StatePublished - Jul 22 2002
Externally publishedYes


  • Mutation
  • PITX2
  • Sequence polymorphism


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