Genetic landscape of preterm birth due to cervical insufficiency: Comprehensive gene analysis and patient next-generation sequencing data interpretation
| Autor: | Dmitrijs Rots, Anna Kornete, Inga Kempa, Linda Gailite, Dace Rezeberga, Ludmila Volozonoka, Anna Miskova |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cervical insufficiency Physiology Maternal Health Cervix Uteri Bioinformatics Biochemistry Cervix 0302 clinical medicine Reproductive Physiology Pregnancy Medicine and Health Sciences 030219 obstetrics & reproductive medicine Multidisciplinary Pregnancy Outcome Obstetrics and Gynecology High-Throughput Nucleotide Sequencing Phenotype Phenotypes medicine.anatomical_structure Cohort Medicine Premature Birth Female Anatomy Genital Anatomy Research Article Adult Science Preterm Birth 03 medical and health sciences Genetic variation Genetics medicine Humans Gene Preterm Labor business.industry Reproductive System Biology and Life Sciences Proteins Computational Biology Correction Human Genetics medicine.disease Human genetics Pregnancy Complications 030104 developmental biology Birth Women's Health business Collagens |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 3, p e0230771 (2020) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0230771 |
| Popis: | Preterm delivery is both a traumatizing experience for the patient and a burden on the healthcare system. A condition distinguishable by its phenotype in prematurity is cervical insufficiency, where certain cases exhibit a strong genetic component. Despite genomic advancements, little is known about the genetics of human cervix remodeling during pregnancy. Using selected gene approaches, a few studies have demonstrated an association of common gene variants with cervical insufficiency. However, until now, no study has employed comprehensive methods to investigate this important subject matter. In this study, we asked: i) are there genes reliably linked to cervical insufficiency and, if so, what are their roles? and ii) what is the proportion of cases of non-syndromic cervical insufficiency attributable to these genetic variations? We performed next-generation sequencing on 21 patients with a clinical presentation of cervical insufficiency. To assist the sequencing data interpretation, we retrieved all known genes implicated in cervical functioning through a systematic literature analysis and additional gene searches. These genes were then classified according to their relation to the questions being posed by the study. Patients’ sequence variants were filtered for pathogenicity and assigned a likelihood of being contributive to phenotype development. Gene extraction and analysis revealed 12 genes primarily linked to cervical insufficiency, the majority of which are known to cause collagenopathies. Ten patients carried disruptive variants potentially contributive to the development of non-syndromic cervical insufficiency. Pathway enrichment analysis of variant genes from our cohort revealed an increased variation burden in genes playing roles in tissue mechanical and biomechanical properties, i.e. collagen biosynthesis and cell-extracellular matrix communications. Consequently, the proposed idea of cervical insufficiency being a subtle form of collagenopathy, now strengthened by our genetic findings, might open up new opportunities for improved patient evaluation and management. |
| Databáze: | OpenAIRE |
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