Relative Frequencies of PAX6 Mutational Events in a Russian Cohort of Aniridia Patients in Comparison with the World’s Population and the Human Genome

Abstract

Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. Here we analyzed the PAX6 gene locus for mutational spectra obtained in our own and previous studies and compared them with data on other genes as well as the whole human genome. MLPA and Sanger sequencing were used for mutation searching in a cohort of 199 index patients from Russia with aniridia and aniridia-related phenotypes. The relative frequencies of different categories of PAX6 mutations were consistent with those previously reported by other researchers. The ratio between substitutions, small indels, and chromosome deletions in the 11p13 locus was within the interval previously published for 20 disease associated genomic loci, but corresponded to a higher end due to very high frequencies of small indels and chromosome deletions. The ratio between substitutions, small indels, and chromosome deletions for disease associated genes, including the PAX6 gene as well as the share of PAX6 missense mutations, differed considerably from those typical for the whole genome.

A bird’s eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases

“…Cross et al applied both direct sequencing and MLPA in a cohort of 434 subjects undergoing diagnostic testing for PAX6 [ 55 ]. Vasilyeva et al, who screened 199 patients for variants at the 11p13 locus, adopted the same analytical approach [ 56 ]. In these works, the diagnostic rate is very different, 58.5% and 69%, respectively, and this is due to the different composition of the cohort (59% vs 92% of patients with classical aniridia).…”

An Unusual Presentation of Novel Missense Variant in PAX6 Gene: NM_000280.4:c.341A>G, p.(Asn114Ser)

“…Molecular genetic analysis of the PAX6 gene was carried out using a published algorithm [14]. During Sanger sequencing, a novel single nucleotide variant, NM_000280.4:c. 341A>G, was identified in a heterozygous state in exon 6 of the PAX6 gene.…”