Novel mutations of the , , and genes cause abnormal development of the iris in Vietnamese individuals.

PURPOSE

Congenital iris abnormality is a feature of several genetic conditions, such as aniridia syndrome and anterior segment degeneration (ASD) disorders. Aniridia syndrome is caused by mutations in the gene or its regulatory elements in the locus 11p13 or deletions of contiguous genes, while ASDs are the result of mutations in various genes, such as , , , and . This study aims to identify pathogenic mutations in Vietnamese individuals with congenital anomalies of the iris.

METHODS

Genomic DNA was extracted from peripheral blood of 24 patients belonging to 15 unrelated families and their available family members. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the deletions or duplications in the 11p13-14 region, including the gene and its neighboring genes. Direct PCR sequencing was used to screen mutations in 13 exons and flanking sequences of the gene. The patients without mutation in the locus were further analyzed with whole exome sequencing (WES). Identified mutations were tested with segregation analysis in proband family members.

RESULTS

We identified a total of 8 novel and 4 recurrent mutations in 20 of 24 affected individuals from 12 families. Among these mutations, one large deletion of the whole gene and another deletion of the downstream region containing the and genes were identified. Eight mutations were detected in , including four nonsense, three frameshift, and one splice site. In addition, two point mutations were identified in the and genes in patients without mutation in . Some of the mutations segregated in an autosomal dominant pattern where family members were available.

CONCLUSIONS

This study provides new data on causative mutations in individuals with abnormal development of iris tissue in Vietnam. These results contribute to clinical management and genetic counseling for affected people and their families.