Genetic Approaches to Differential Diagnosis of Hereditary Forms of Congenital Aniridia

Abstract

Congenital aniridia (AN) is a hereditary autosomal dominant developmental disorder of the eye. Heterozygous mutations in the PAX6 gene and chromosomal rearrangements involving the 11p13 locus lie behind the pathogenesis of the AN. The key role of the PAX6 gene in the regulation of embryogenesis and the pleiotropic effect of this transcription factor explain the damage of several tissues of the anterior and posterior segments of the eye, brain structures, and the disturbance of morphogenesis and endocrine function of the pancreas observed in AN. Recently AN has been considered a syndromic pathology by several researchers. The review suggests classification and summarizes information on the clinical characteristics and genetic basis of various forms of AN. The problem of discrimination of clinical-genetic variants of the dysgenesis of the anterior segment of the eye and the differential diagnosis of PAX6-associated AN with WAGR syndrome, anterior dysgenesis, other rare monogenic and chromosomal syndromes is discussed, and the role of molecular diagnostics is emphasized.

Upstream ORF frameshift variants in thePAX65ʹUTR cause congenital aniridia

“…The diagnosis of patients was based on the clinical presentation that comprised bilateral aniridia, foveal hypoplasia, accompanied by sensory deficient congenital nystagmus, cataract, and keratopathy. A combination of PAX6 Sanger sequencing, followed by MLPA analysis of 11p13 locus was undertaken as described previously (Vasilyeva, Voskresenskaya, Khlebnikova, et al, 2017).…”

Functional reassessment of PAX6 single nucleotide variants by in vitro splicing assay

“…Congenital aniridia is a rare autosomal dominant panocular disorder. Loss-of-function nucleotide variants and haploinsufficiency of the PAX6 gene is thought to be the main mechanism of congenital aniridia etiopathogenesis [1]. Nevertheless, true functional consequences of different types of PAX6 variants, which could include effects on splicing, are still in question.…”

A sporadic case of congenital aniridia caused by pericentric inversion inv(11)(p13q14) associated with a 977 kb deletion in the 11p13 region

“…Aniridia (OMIM #106210 [1]) is a Mendelian autosomal dominant complex congenital developmental disorder that can affect all eye structures as well as central nervous system, the endocrine system, and other systems and organs [2,3]. Congenital aniridia (AN) is caused by heterozygous mutations in the PAX6 gene (OMIM *607108; 11p13) or 11p13 deletions.…”