Case report

Identification of the first intragenic deletion of the PITX2 gene causing an Axenfeld-Rieger Syndrome: case report

Guillaume de la Houssaye¹ , Ivan Bieche² , Olivier Roche^1,3 , Véronique Vieira¹ , Ingrid Laurendeau² , Laurence Arbogast¹ , Hatem Zeghidi³ , Philippe Rapp³ , Philippe Halimi⁴ , Michel Vidaud² , Jean-Louis Dufier^1,3 , Maurice Menasche¹ and Marc Abitbol^1,3

¹Centre de Recherche Thérapeutique en Ophtalmologie, EA n°2502, Faculté de Médecine René Descartes, site Necker, 156 rue de Vaugirard 75730 Paris cedex 15, Université Paris V, Paris, France

²Laboratoire de Génétique Moleculaire-INSERM U745, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France

³CHU Necker Enfants Malades, Service d'ophtalmologie, 149, rue de Sèvres 75 Paris cedex 15, France

⁴Service de radiologie et d'imagerie médicale de Hôpital Européen Georges Pompidou, 20-40 Rue Leblanc, 75908 Paris Cedex 15, France

author email corresponding author email

BMC Medical Genetics 2006, 7:82doi:10.1186/1471-2350-7-82

Published:	29 November 2006

Abstract

Background

Axenfeld-Rieger syndrome (ARS) is characterized by bilateral congenital abnormalities of the anterior segment of the eye associated with abnormalities of the teeth, midface, and umbilicus. Most cases of ARS are caused by mutations in the genes encoding PITX2 or FOXC1. Here we describe a family affected by a severe form of ARS.

Case presentation

Two members of this family (father and daughter) presented with typical ARS and developed severe glaucoma. The ocular phenotype was much more severe in the daughter than in the father. Magnetic resonance imaging (MRI) detected an aggressive form of meningioma in the father. There was no mutation in the PITX2 gene, determined by exon screening. We identified an intragenic deletion by quantitative genomic PCR analysis and characterized this deletion in detail.

Conclusion

Our findings implicate the first intragenic deletion of the PITX2 gene in the pathogenesis of a severe form of ARS in an affected family. This study stresses the importance of a systematic search for intragenic deletions in families affected by ARS and in sporadic cases for which no mutations in the exons or introns of PITX2 have been found. The molecular genetics of some ARS pedigrees should be re-examined with enzymes that can amplify medium and large genomic fragments.