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


METHODS
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.


CONCLUSIONS
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.
de la Houssaye
Guillaume
G
Centre de Recherche Thérapeutique en Ophtalmologie, EA no 2502, Faculté de Médecine René Descartes, site Necker, 156 rue de Vaugirard 75730 Paris cedex 15, Université Paris V, Paris, France. delaho@necker.fr
Bieche
Ivan
I
Roche
Olivier
O
Vieira
Véronique
V
Laurendeau
Ingrid
I
Arbogast
Laurence
L
Zeghidi
Hatem
H
Rapp
Philippe
P
Halimi
Philippe
P
Vidaud
Michel
M
Dufier
Jean-Louis
JL
Menasche
Maurice
M
Abitbol
Marc
M
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000869:Anterior Eye Segment / Q000002:abnormalities; D001483:Base Sequence; D004252:DNA Mutational Analysis / Q000379:methods; D004587:Electrophoresis, Agar Gel; D005124:Eye Abnormalities; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009900:Optic Nerve / Q000002:abnormalities; D010375:Pedigree; D013577:Syndrome; D014071:Tooth Abnormalities; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2