DO: 0112278;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 21q22.3 | Premature ovarian failure 19 | 619245 | Autosomal recessive | 3 | HSF2BP | 604554 |
A number sign (#) is used with this entry because of evidence that premature ovarian failure-19 (POF19) is caused by homozygous mutation in the HSF2BP gene (604554) on chromosome 21q22. One such family has been reported.
Premature ovarian failure-19 (POF19) is characterized by irregular menses that cease in the third decade of life, associated with infertility (Felipe-Medina et al., 2020).
For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360).
Felipe-Medina et al. (2020) reported a consanguineous Israeli Arab family in which 3 of 5 sisters (III-1, III-2, and III-3), including a monozygotic twin pair, had early secondary amenorrhea. The affected twins had normal onset of menstruation at 13 to 14 years of age, but menses were irregular and ceased around age 25. Ultrasound of 1 of the twins (III-1) showed normal uterus and ovaries. The twins' older sister (III-3), who was diagnosed with premature ovarian failure, underwent fertility treatment and had 1 normal pregnancy; a second attempt was unsuccessful. Clinical details for that patient were unavailable. The affected individuals also had 2 fertile sisters and 1 fertile brother. In addition, a maternal great-aunt was reported to have POF.
The transmission pattern of POF19 in the family reported by Felipe-Medina et al. (2020) was consistent with autosomal recessive inheritance.
By whole-exome sequencing in a consanguineous Israeli Arab family in which 3 sisters had premature ovarian failure, Felipe-Medina et al. (2020) identified homozygosity for a missense mutation in the HSF2BP gene (S167L; 604554.0001) that segregated fully with disease. The authors noted that there were no homozygous males in the family, and thus the impact of the variant on male fertility could not be analyzed.
Felipe-Medina, N., Caburet, S., Sanchez-Saez, F., Condezo, Y. B., de Rooij, D. G., Gomez-H, L., Garcia-Valiente, R., Todeschini, A. L., Duque, P., Sanchez-Martin, M. A., Shalev, S. A., Llano, E., Veitia, R. A., Pendas, A. M. A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1. eLife. 9: e56996, 2020. Note: Electronic Article. [PubMed: 32845237] [Full Text: https://doi.org/10.7554/eLife.56996]