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Mutations in eIF4ENIF1 Are Associated With Primary Ovarian Insufficiency.
| Publication Type | Journal Article |
| Authors | Kasippillai, T., Macarthur DG, Kirby A., Thomas B., Lambalk CB, Daly M. J., and Welt CK |
| Abstract | 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 measured.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. |
| Year of Publication | 2013 |
| Journal | The Journal of clinical endocrinology and metabolism |
| Date Published (YYYY/MM/DD) | 2013/07/31 |
| ISSN Number | 0021-972X |
| DOI | 10.1210/jc.2013-1102 |
| PubMed | http://www.ncbi.nlm.nih.gov/pubmed/23902945?dopt=Abstract |
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