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

Int J Mol Sci 2019 Nov 28;20(23). Epub 2019 Nov 28.

Center for Medical Genomics-OMICRON, Jagiellonian University Medical College, ul. Kopernika 7c, 31-034 Krakow, Poland.

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 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 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 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.

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20236006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928627PMC
November 2019

Publication Analysis

Top Keywords

text mining
12
variant filtering
8
genetic variants
8
peters syndrome
8
automatic text
8
guidelines helped
4
helped find
4
find compound
4
2015 guidelines
4
acmg 2015
4
compliance acmg
4
compound heterozygous
4
sequencing data
4
data compliance
4
gene
4
phenotype peters
4
syndrome pps
4
pps second
4
second nm_1943183c755delc
4
associated phenotype
4

Similar Publications

Peters plus syndrome and Chorioretinal findings associated with B3GLCT gene mutation - a case report.

BMC Ophthalmol 2020 Mar 23;20(1):118. Epub 2020 Mar 23.

Bascom Palmer Eye Institute, University of Miami, 900 NW 17th St, Miami, FL, 33136, USA.

Background: Peters plus syndrome (PPS) is a combination of congenital Peters anomaly and systemic abnormalities. It is inherited most commonly in an autosomal recessive pattern with homozygous B3GLCT mutations. Ocular findings consist predominantly anterior segment abnormalities without posterior segment involvement. Read More

View Article and Full-Text PDF
March 2020

Peters plus syndrome mutations disrupt a noncanonical ER quality-control mechanism.

Curr Biol 2015 Feb 24;25(3):286-295. Epub 2014 Dec 24.

Department of Biochemistry and Cell Biology, 450 Life Sciences Building, Stony Brook University, Stony Brook, NY 11794-5215, USA. Electronic address:

Background: O-fucose is added to cysteine-rich domains called thrombospondin type 1 repeats (TSRs) by protein O-fucosyltransferase 2 (POFUT2) and is elongated with glucose by β3-glucosyltransferase (B3GLCT). Mutations in B3GLCT result in Peters plus syndrome (PPS), an autosomal recessive disorder characterized by eye and other developmental defects. Although 49 putative targets are known, the function of the disaccharide and its role in PPS remain unexplored. Read More

View Article and Full-Text PDF
February 2015

Novel B3GALTL mutations in classic Peters plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes.

Clin Genet 2014 Aug 17;86(2):142-8. Epub 2013 Sep 17.

Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, WI, USA; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

Peters plus syndrome (PPS) is a rare autosomal-recessive disorder characterized by Peters anomaly of the eye, short stature, brachydactyly, dysmorphic facial features, developmental delay, and variable other systemic abnormalities. In this report, we describe screening of 64 patients affected with PPS, isolated Peters anomaly and PPS-like phenotypes. Mutations in the coding region of B3GALTL were identified in nine patients; six had a documented phenotype of classic PPS and the remaining three had a clinical diagnosis of PPS with incomplete clinical documentation. Read More

View Article and Full-Text PDF
August 2014

Clinical utility gene card for: Peters plus syndrome.

Eur J Hum Genet 2016 08 6;24(8). Epub 2016 Apr 6.

Centre for Human Genetics, KU Leuven, Leuven, Belgium.

View Article and Full-Text PDF
August 2016