Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations

Objective To identify new molecular actors involved in nonsyndromic premature ovarian failure (POF) etiology. Design This is a retrospective case-control cohort study. Setting University research group and IVF medical center. Patient(s) Twelve women affected by nonsyndromic POF. The control group in...

Full description

Autores:
Tipo de recurso:
Fecha de publicación:
2015
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/24058
Acceso en línea:
https://doi.org/10.1016/j.fertnstert.2015.04.016
https://repository.urosario.edu.co/handle/10336/24058
Palabra clave:
Adamts19 gene
Adult
Article
Bioinformatics
Bmpr2 gene
Case control study
Cohort analysis
Computer model
Female
Gene
Gene mutation
Gene sequence
Human
Lhcgr gene
Major clinical study
Menopause
Next generation sequencing
Phenotype
Premature ovarian failure
Priority journal
Retrospective study
Sanger sequencing
Genetics
High throughput sequencing
Mutation
Primary ovarian insufficiency
Procedures
Sequence analysis
Adam protein
Bone morphogenetic protein receptor 2
Adam proteins
Adult
Case-control studies
Cohort studies
Female
High-throughput nucleotide sequencing
Humans
Mutation
Primary ovarian insufficiency
Retrospective studies
Sequence analysis
Adamts19
Bmpr2
Next generation sequencing
Pof
Premature ovarian failure
human
human
type ii
Adamts19 protein
Bmpr2 protein
Bone morphogenetic protein receptors
Rights
License
Abierto (Texto Completo)
Description
Summary:Objective To identify new molecular actors involved in nonsyndromic premature ovarian failure (POF) etiology. Design This is a retrospective case-control cohort study. Setting University research group and IVF medical center. Patient(s) Twelve women affected by nonsyndromic POF. The control group included 176 women whose menopause had occurred after age 50 and had no antecedents regarding gynecological disease. A further 345 women from the same ethnic origin (general population group) were also recruited to assess allele frequency for potentially deleterious sequence variants. Intervention(s) Next generation sequencing (NGS), Sanger sequencing, and bioinformatics analysis. Main Outcome Measure(s) The complete coding regions of 70 candidate genes were massively sequenced, via NGS, in POF patients. Bioinformatics and genetics were used to confirm NGS results and to identify potential sequence variants related to the disease pathogenesis. Result(s) We have identified mutations in two novel genes, ADAMTS19 and BMPR2, that are potentially related to POF origin. LHCGR mutations, which might have contributed to the phenotype, were also detected. Conclusion(s) We thus recommend NGS as a powerful tool for identifying new molecular actors in POF and for future diagnostic/prognostic purposes. © 2015 American Society for Reproductive Medicine.