Genetic analysis of a Chinese family with congenital aniridia and detection of PAX6 mutation locus

Background

Congenital aniridia is a rare bilateral hereditary ophthalmopathy which impact panocular.Researches showed that congenital aniridia can be caused by different mutation locus of PAX6 genes, and the mutations are multifarious.

Objective

This study was to detect and analyze the mutations of a Chinese family with congenital aniridia by using targeted sequence capture sequencing and direct Sanger sequencing.

Methods

This study was approved by Ethic Committee of the First Affiliated Hospital of Zhengzhou University and followed Declaration of Helsinki.Written informed consent was obtained from subjects or their custodians before any related medical examination.A cross-sectional study was performed.A Chinese congenital aniridia family was included at the First Affiliated Hospital of Zhengzhou University in March, 2016.All the family members received systemic medical examinations including nervous system and oral glucose tolerance test and then the ocular examinations were carried out.The periphery blood of 10 ml was collected from the members for genomic DNA extraction.Targeted sequence capture sequencing was performed on the DNA of proband to screen out the suspicious mutant locus.The mutation was verified by comparing the Sanger direct sequencing results from all family members.

Results

A total of 3 generations of 9 members were included in this congenital aniridia pedigree, and the Ⅰ1 was dead without eye abnormality.Three patients (Ⅱ2 and her children Ⅲ1, Ⅲ2) and 5 normal family members were determined, showing an autosomal dominant inheritance pattern.No abnormal signs were found in nervous system and oral glucose tolerance test in the families.The reduce of visual acuity, ocular hypertension (21 mmHg), absence of biocular iris, opacification of corneal stroma, horizontal nystagmus, hapoplasia of fovea were found in all the sufferers.In addition, the ptosis of the left eye, congenital cataract of the right eye in Ⅱ2 patient as well as biocular cataract and subluxation of lenses also were exhibited.The c. 183C>A mutation of the PAX6 gene was screened out to be a possible pathogenic mutation.The result of Sanger direct sequencing in the families verified a co-segregation of this mutation with mutant phenotypes.

Conclusions

PAX6 gene c. 183C>A, a rare mutation in Chinese population, is a virulence mutation site in this aniridia family.

Aniridia/genetics; Chromosomes, human, pair 11/genetics; Paired box transcription factor 6/genetics; Pedigree; Chinese/genetics; Targeted sequence capture sequencing; Nonsense mutation