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Sequence variant in the CDC42BPB gene is potentially associated with Mullerian duct anomalies
Author(s) -
Luo LiJing,
Feng Fan,
Li ShengHui,
Lu Dan,
Li Lin,
Zhou Qi
Publication year - 2020
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.14211
Subject(s) - sanger sequencing , exome sequencing , genetics , in silico , whole genome sequencing , gene , biology , exome , mutation , sequence analysis , dna sequencing , genome
Aim Mullerian duct anomalies (MDA) are common female genital tract malformations. Genetic and environmental factors are important causes of MDA in women. Although many genes and mutations have been found to be associated with the pathogenesis of MDA, in most cases, the genetic pathogenic factors of MDA are still unknown. Methods We first analyzed the three sisters using low coverage whole‐genome sequencing. Then whole‐exome sequencing was carried out in each patient. The identified sequence variant was confirmed by Sanger sequencing. In silico pathogenicity analysis and conservative analysis of the mutation site were also performed. Protein structural modeling was used to analyze the effect of the mutated amino acid. Results We first analyzed the three sisters with septate uterus using low coverage whole‐genome sequencing, but no possible pathogenic copy number variation was found. Then whole‐exome sequencing was performed on the three sisters, and a rare homozygous variant, CDC42BPB :c.2012G>A:p.R671Q, was identified. All three patients were found with this variant. Sanger sequencing validated that this variant was segregated within the family. In silico pathogenicity analysis and conservative analysis of the mutation site suggested that the variant might be damaging. Protein structural analysis suggested that R671Q might weaken the electrostatic potential of this region, which may be a significant regulation target or protein interaction surface of CDC42BPB. Conclusion We demonstrated that CDC42BPB genetic variant might be potentially associated with the pathogenesis of MDA.