Novel PAX6 variant in a family with ophthalmologic, pancreatic, and olfactory features

Abstract

Variants in the PAX6 gene have been associated with ophthalmologic, neurologic, and pancreatic differences. We report on a proband, mother, and affected brother who presented with congenital cataracts and glaucoma at a young age. Non-ocular findings are also reported among these family members. After a congenital cataracts next generation sequencing (NGS) gene panel was found to be non-diagnostic in 2016, a more expanded panel in 2020 revealed a novel variant: c.178T>A; p.Tyr60Asn in exon 6 of the PAX6 gene in the proband. The variant is also present in the affected mother and affected brother; it is absent in an unaffected brother. The clinical findings of these three relatives, in conjunction with their genetic testing and the associated PAX6 features reported in the literature, suggest that this novel familial variant may be an underlying etiology for these individuals' ophthalmologic, pancreatic, and olfactory symptoms.

A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family

“…Loss of function variants-including frameshift, nonsense, and splicing site mutations-of PAX6 are the most common cause of classic aniridia, which is more likely to be associated with severely affected individuals [1,[4][5][8][9]28] . Milder iris abnormalities are typically attributed to missense mutations [3,17,[28][29] . Observations of patients with less severely affected irises in this study are thus classified as atypical aniridia.…”