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http://purl.uniprot.org/citations/23902945http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23902945http://www.w3.org/2000/01/rdf-schema#comment"

Context

Primary ovarian insufficiency (POI), or premature ovarian failure, results from ovarian follicle depletion with a consequent elevation of FSH levels before age 40 years. We identified a family in which 9 women in 3 consecutive generations developed menopause at approximately age 30 years. We hypothesized a genetic cause with a dominant mode of inheritance.

Design

This was a family-based genetic study and a replicate group of women with POI.

Setting

The study was conducted at an academic medical center.

Patients

Seven affected women and an obligate carrier and 7 unaffected family members were genotyped. The genes of interest were also sequenced in 38 unrelated women with POI.

Intervention

The DNA from 7 family members was subjected to whole-exome sequencing. The genotypes of interest were confirmed and genotypes of additional family members and unrelated women with POI were determined using Sanger sequencing.

Main outcome measure

A high-impact, deleterious variant that segregated appropriately with POI in the family was required.

Results

A heterozygous stop codon (Ser429X) was identified in the eukaryotic translation initiation factor 4E nuclear import factor 1 (eIF4ENIF1) in the proband and all affected women but not in the unaffected family members. The chance that such a high-impact, deleterious variant would segregate appropriately among the affected and unaffected relatives by chance is very low (P < .05). There were no additional mutations identified in eIF4ENIF1 or eIF4E in 38 unrelated women with POI.

Conclusion

Data demonstrate a new gene associated with dominantly inherited POI. These results highlight the importance of translation initiation factors and their regulators in ovarian function."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.org/dc/terms/identifier"doi:10.1210/jc.2013-1102"xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/author"Daly M.J."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/author"Thomas B."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/author"MacArthur D.G."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/author"Kirby A."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/author"Welt C.K."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/author"Lambalk C.B."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/author"Kasippillai T."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/pages"E1534-9"xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/title"Mutations in eIF4ENIF1 are associated with primary ovarian insufficiency."xsd:string
http://purl.uniprot.org/citations/23902945http://purl.uniprot.org/core/volume"98"xsd:string
http://purl.uniprot.org/citations/23902945http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23902945
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