Rieger syndrome is not associated with PAX6 deletion: a correction to Acta Ophthalmol Scand 2001: 79: 201–203

Abstract

Editor, Rieger syndrome is a rare autosomal-dominant disorder comprising iris stroma hypoplasia with strands of iris tissue crossing the anterior chamber angle (Axenfeld–Rieger anomaly). Schwalbe’s line may be anteriorly displaced (posterior embryotoxon). Non-ocular findings in Rieger syndrome are typical facial and dental anomalies and redundant periumbilical skin. The ocular anomalies are often complicated by glaucoma. In 2001, Riise and coworkers published a case study of the typical phenotype of Rieger syndrome, in which fluorescent in situ hybridisation (FISH) analysis showed a heterozygous deletion on chromosome 11p13 including the PAX6 gene (Riise et al. 2001; Riise 2005). This deletion was not found in the parents. However, a deletion of PAX6 in Rieger syndrome has not been reported by any other investigators. Therefore, we felt that it was relevant to repeat testing of this patient in order to confirm the initial finding. Three laboratories were involved, including the laboratory where the original results were found. None of the three laboratories could confirm the PAX6 deletion described originally using different methods [multiplex ligation-dependent probe amplification (MLPA) and FISH]. Because we found differently sized signals for the originally used PAX6 probe by repeated FISH analysis (Kennedy Centre), we suspect that poor hybridization was the cause for the erroneous diagnosis. We did not find any deletion of PAX6 in 30 metaphases analysed by FISH, which makes mosaicism unlikely. Furthermore, one laboratory found a known PITX2 mutation c.253-11A>G, which has been described previously in Rieger syndrome, thus confirming the clinical diagnosis (Semina et al. 1996; Borges et al. 2002). This mutation has been confirmed in a second laboratory. Although c.253-11A>G is a known mutation with presumed pathogenic effect, the PITX2 mutation was not found in an analysis of 100 normal individuals. Segregation testing in the parents indicated a de novo origin. In conclusion, because the original finding could not be confirmed in Rieger syndrome, the presumption that PAX6 changes (deletions) might lead to classic Rieger syndrome should be revised.