Purpose: Aniridia is phenotypically and genetically heterogeneous. This study is to summarize the phenotypes and identify the underlying genetic cause of the paired box 6 (PAX6) gene responsible for aniridia in two three-generation Chinese families in northern China.
Methods: A detailed family history and clinical data were collected from patients during an ophthalmologic examination. All exons and flanking intronic sequences of the PAX6 gene were amplified with PCR and screened for mutation with direct DNA sequencing. Haplotyping was used to confirm the mutation sequence. Real-time PCR was used to determine the PAX6 messenger ribonucleic acid(mRNA) level in patients with aniridia and in unaffected family members.
Results: The probands and other patients in the two families were affected with aniridia accompanied with or without congenital cataract. A heterozygous PAX6 mutation in exon 5 (c.112delC, p.Arg38GlyfsX16) was identified in FAMILY-1, which was predicted to generate a frameshift and created a premature termination codon. A heterozygous PAX6 mutation in exon 7 (c.362C>T, p.Ser121Leu) was identified in FAMILY-2. Each mutation cosegregated with the affected individuals in the family and did not exist in unaffected family members and 200 unrelated normal controls. The PAX6 messenger ribonucleic acid level was about 50% lower in patients with aniridia than in unaffected family members in FAMILY-1.
Conclusions: The deletion mutation (c.112delC) in the PAX6 gene was first identified in a Chinese family with aniridia, congenital progressive cataract, developmental delay, or the absence of ulna. The mutation (c.362C>T, p.Ser121Leu) in the PAX6 gene was first identified in a patient with aniridia with congenital ptosis. We summarized the variable phenotypes among the patients, which expanded the phenotypic spectrum of aniridia in a different ethnic background.