Faculty Collaboration Database

Exclusion of PITX2 mutations as a major cause of CHARGE association. Am J Med Genet 2002 Jul 22;111(1):27-30

Date

07/19/2002

Pubmed ID

12124729

DOI

10.1002/ajmg.10473

Scopus ID

2-s2.0-4243288689 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

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.

Author List

Martin DM, Probst FJ, Fox SE, Schimmenti LA, Semina EV, Hefner MA, Belmont JW, Camper SA

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

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

Abnormalities, Multiple
Choanal Atresia
Coloboma
DNA Mutational Analysis
Deafness
Ear
Female
Gene Expression Regulation, Developmental
Genitalia
Growth Disorders
Heart Defects, Congenital
Homeodomain Proteins
Humans
Male
Nuclear Proteins
Phenotype
Polymorphism, Genetic
Syndrome
Transcription Factors