Two Paired Box 6 mutations identified in Chinese patients with classic congenital aniridia and cataract

Abstract

Congenital aniridia is a rare genetic disorder characterized by a variable degree of hypoplasia or absence of iris. It is frequently associated with keratopathy, cataract, juvenile-onset glaucoma and foveal and optic nerve hypoplasia. Mutations in the Paired Box 6 (PAX6) gene on chromosome 11p13 have been demonstrated to cause aniridia. The aim of the present study was to investigate the genetic variations of PAX6 in two sporadic patients from southern China with classic congenital aniridia and cataract. Complete ophthalmic and physical examinations were performed, including best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus examination, optical coherence tomography, ultrasound biomicroscopy, and Pentacam scanning. Genomic DNA was extracted from leukocytes of peripheral blood collected from the two patients, their unaffected parents and 200 unrelated control subjects from the same population. Exons 4–13 of the PAX6 gene were amplified by polymerase chain reaction and sequenced directly. Patient 1 was affected with aniridia accompanied by congenital cataract and nystagmus. A novel heterozygous PAX6 frameshift mutation c.277delG (p.Glu93SerfsX31) in exon 6 was identified in this patient. Patient 2 was presented with aniridia, congenital cataract, lens subluxation and glaucoma. A recurrent nonsense mutation c.718C>T (p.Arg240X) in exon 9 was identified in this patient. The present results expand the mutation spectrum of PAX6 and will be valuable for genetic counseling in the affected families. Additionally, the identification of these mutations reiterates the importance of PAX6 in ocular development and sheds light on the pathogenesis of congenital aniridia.

A Novel Mutation in CRYGC Mutation Associated with Autosomal Dominant Congenital Cataracts and Microcornea

“…Previous studies 12,17, have identified several mutations in the CRYGC gene . Moreover, there have been previous reports 48,49 regarding frameshift mutations in CRYGC. However, we report the novel CRYGC frameshift mutation c.389_390insGCTG (p.C130fs) in exon 3,…”

The Genetic and Endoplasmic Reticulum-Mediated Molecular Mechanisms of Primary Open-Angle Glaucoma

“…Furthermore, Mayer et al have shown that glaucoma has been identified in 52% out of 80 patients with congenital aniridia [187]. Lin et al have demonstrated that aniridia associated with glaucoma, congenital cataract, and lens subluxation may be caused by the recurrent nonsense mutation c.718C > T (p.Arg240X) in exon 9 of the PAX6 gene [188]. It has also been demonstrated that loss of PAX6 expression may cause an aniridia occurrence [189][190][191].…”

Clinical and Genetic Landscape of Ectopia Lentis Based on a Cohort of Patients From 156 Families

“… 8 In addition to these seven genes, which have been widely reported and recognized as the causal genes for EL, there are also seven additional genes that have been reported to cause syndromes that include EL. ASPH is related to Traboulsi syndrome, 9 – 12 COL18A1 is related to Knobloch syndrome, 13 CPAMD8 is related to anterior segment dysgenesis, 14 PAX6 is related to aniridia, 15 VSX2 is related to microphthalmia, 16 TGFB2 is related to Loeys–Dietz syndrome, 17 and MTHFR is related to homocystinuria. 18 Variants in these genes with lens subluxation were reported sporadically.…”