Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining

Abstract

Anterior segment dysgenesis (ASD) encompasses a spectrum of ocular disorders affecting the structures of the anterior eye chamber. Mutations in several genes, involved in eye development, are implicated in this disorder. ASD is often accompanied by diverse multisystemic symptoms and another genetic cause, such as variants in genes encoding collagen type IV. Thus, a wide spectrum of phenotypes and underlying genetic diversity make fast and proper diagnosis challenging. Here, we used AMELIE, an automatic text mining tool that enriches data with the most up-to-date information from literature, and wANNOVAR, which is based on well-documented databases and incorporates variant filtering strategy to identify genetic variants responsible for severely-manifested ASD in a newborn child. This strategy, applied to trio sequencing data in compliance with ACMG 2015 guidelines, helped us find two compound heterozygous variants of the B3GLCT gene, of which c.660+1G>A (rs80338851) was previously associated with the phenotype of Peters plus syndrome (PPS), while the second, NM_194318.3:c.755delC (p.T252fs), in exon 9 of the same gene was noted for the first time. PPS, a very rare subtype of ASD, is a glycosylation disorder, where the dysfunctional B3GLCT gene product, O-fucose-specific β-1,3-glucosyltransferase, is ineffective in providing a noncanonical quality control system for proper protein folding in cells. Our study expands the mutation spectrum of the B3GLCT gene related to PPS. We suggest that the implementation of automatic text mining tools in combination with careful variant filtering could help translate sequencing results into diagnosis, thus, considerably accelerating the diagnostic process and, thereby, improving patient management.

In Silico Analysis of B3GALTL Gene Reveling 13 Novel Mutations Associated with Peters’-plus syndrome

“…Previous researches reported c.660+1G>A(rs80338851) as the most common mutation in Peters plus syndrome (PPS)(12, 22). While other work done by Weh et al reported different types of mutations, one of them is a missense mutation (G394E) which was also reported to have deleterious effect in our analysis by the first four soft wares (SIFT, Provean,Polyphen2 and SNAP2).…”

“…Until now the molecular processes that leads to the signs and symptoms of the syndrome is still not well undrestood,(11) but impaired glycosylation likely disrupts the function of the proteins, which may contribute to the variety of features. (12) Absent mutation in B3GLCT gene in the present of other typical symptoms and sign are termed Peters plus-like syndrome. (13, 14)…”

Targeted sequencing of a gene panel in patients with Familial Hypercholesterolemia from Southern Poland

“…Raw reads were processed with the Illumina software, generating demultiplexed fast files with base calls and corresponding base-call quality scores. These files were then processed through a custom pipeline that in detail was described in our previous publication [12]. Briefly, the quality of reads was assessed with the FastQC v.11.5.…”