A Chinese family with Axenfeld-Rieger syndrome: report of the clinical and genetic findings.

AIM

To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome (ARS) and characterize the molecular defect in in the family.

METHODS

Patients presented with typical ARS from a Chinese family were investigated. We performed genome-wide linkage scan and exome sequencing to identify the pathogenic mutations. Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to verify the expression of the pathogenic gene.

RESULTS

Genome-wide linkage and exome sequencing analyses showed as the disease candidate gene. A>G substitution at position -11 of 3'ss of exon 5 (IVS5-11A>G) that co-segregated with the disease phenotype was discovered in the family. The messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family.

CONCLUSION

Our findings implicate the first intronic mutation of the gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of have been found.