Pathogenic variants of BUB1 and BUBR1 genes are not prioritized in screening tests of couples with aborted aneuploid fetuses

TL;DR

This study found that specific harmful genetic variants in BUB1 and BUBR1 genes are not present in couples who had miscarriages due to aneuploid fetuses.

Contribution

The study demonstrates that certain BUB1 and BUBR1 pathogenic variants are not relevant for screening in couples with a history of aneuploid miscarriages.

Findings

No homozygous or heterozygous pathogenic variants of BUB1 and BUBR1 were found in 50 aneuploid fetal samples.

The allele frequencies of the studied variants were zero in the analyzed population.

These variants are not recommended for routine screening in couples with a history of aneuploid miscarriages.

Abstract

Chromosome aberrations certainly aneuploidie are the cause of the majority of spontaneous abortions in humans. BUB1 (budding uninhibited by benzimidazole 1) and BUBR1 (BUB1 mitotic checkpoint serine/threonine kinase B) are two key proteins mediating spindle-checkpoint activation that play a role in the inhibition of the anaphase-promoting complex/ cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. This study aimed to evaluate the probable roles of BUB1 and BUBR1 pathogenic variants in abortion of the fetuses with aneuploidy. Fifty aborted fetuses with approved aneuploidy using array comparative genomic hybridization (aCGH) were included. BUB1 and BUBR1 genes were studied using the Sanger sequencing for the single nucleotide variant (SNV) detection, certainly rs121909055 and rs28989185 as the pathogenic target variants. The sequencing results were analyzed by finch TV software.Neither homozygous nor heterozygous variant of the targeted SNVs was observed in the samples. No other SNV was detectable in the analyzed parts of the BUB1 and BUBR1 genes in all samples. Since the allele frequencies of the variants of interest were zero in 50 studied samples, these SNVs would not be prioritized for screening in the parents with a history of miscarriage due to aneuploidy.