Abstract
Objective
Peters Plus syndrome (PTRPLS<strong>)</strong> is an autosomal recessive congenital disorder of glycosylation caused by biallelic pathogenic variants in the ß 1,3-glucosyltransferase gene (B3GLCT). To date, homozygous or compound heterozygous splicing, truncating, missense variants, and whole gene deletions have been reported in the B3GLCT gene. This study aims to emphasize the role of small copy number variations (CNVs) in this condition alongside the clinical features of the patients.
Methods
The study included eleven patients from six consanguineous families originating from the same village. Clinical exome sequencing-based CNV analysis was employed across all probands to ascertain the genetic background.
Results
Using GATK-gCNV, we identified a homozygous deletion on chromosome 13q12.3, encompassing 15<sup>th </sup>exon of the B3GLCT gene. The mean age at admission was 9.6 ± 13.3 years, ranging from 2 months to 41 years. The mean standart deviation (SD) scores for height and weight at admission were -4.4 ± 0.9 and -3.8 ± 1.8, respectively. Ophthalmological abnormalities included corneal haze, anterior synechiae, unilateral leucoma, corneal-lenticular adhesion, glaucoma, and severe visual loss. Patients under the age of five exhibited global developmental delay, while those older than five years demonstrated varying degrees of intellectual disability, with two exceptions exhibiting normal cognitive function.
Conclusion
Our findings underscore the critical role of NGS-based CNV analysis in improving the diagnostic accuracy of PTRPLS. CNVs represent a significant form of genomic variation and should be systematically considered in genetically unresolved Mendelian disorders. Integrating CNV detection algorithms into routine NGS diagnostic workflows has the potential to enhance the identification of pathogenic variants, ultimately facilitating a more comprehensive molecular diagnosis for affected individuals<strong>.</strong>
