Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0033377 (
prolapse
)
11,717
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pelvic organ
prolapse
(
POP
) is a common gynecological disorder; however, the genetic components remain largely unidentified. Exome sequencing has been widely used to identify pathogenic gene mutations of several diseases because of its high chromosomal coverage and accuracy. In this study, we performed whole exome sequencing (WES), for the first time, on 8 peripheral blood DNA samples from representative
POP
cases. After filtering the sequencing data from the dbSNP database (build 138) and the 1000 Genomes Project, 2 missense variants in
WNK1
, c.2668G > A (p.G890R) and c.6761C> T (p.P2254L), were identified and further validated via Sanger sequencing. In validation stage, the c.2668G > A (p.G890R) variant and 8 additional variants were detected in 11 out of 161
POP
patients. All these variants were absent in 231 healthy controls. Functional experiments showed that fibroblasts from the utero-sacral ligaments of
POP
with
WNK1
mutations exhibited loose and irregular alignment compared with fibroblasts from healthy controls. In sum, our study identified a novel gene,
WNK1
, for
POP
susceptibility, expanded the causal mutation spectrums of
POP
, and provided evidence for the genetic diagnosis and medical management of
POP
in the future.
...
PMID:Exome sequencing identifies a novel gene, WNK1, for susceptibility to pelvic organ prolapse (POP). 2573 19
