Identification of a Novel Four-basepair Deletion in a Rieger Syndrome Family

Methods: Two families with a total of 15 persons including 7 patients affected by Rieger syndrome were recruited for this study. At least one of the affected individuals in each family manifested all three cardinal features of Rieger syndrome: tooth agenesis, ocular anterior segment dysgenesis, and umbilical stump abnormalities. Single-strand conformation polymorphism (SSCP) analysis was performed to screen mutations in PITX2 gene, followed by direct sequencing of the PCR products of the entire homoebox region, and subclone sequencing was used to identify the exact status of mutation.

Results: We identified a novel four-basepair deletion, 717-720 in exon 3 within the homeobox of PITX2 gene in each patients of a three-generation family. The mutation was not found in the healthy relatives in the same family and those members in another Rieger syndrome family. The deletion occurs at the beginning of the homoebox, causes a frame shift and introduces a premature stop codon in the gene sequence.

Conclusion: Our finding indicates that the novel four-basepair deletion mutation in PITX2, resulting in a truncated peptide, is responsible for the large Chinese family of Rieger syndrome. The detection of this mutation could be applied in prenatal diagnosis for the family. Furthermore, our study also shows the presence of genetic heterogeneity of Rieger syndrome.