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, 5 (6), e11282

Clinical, Biological and Genetic Analysis of Prepubertal Isolated Ovarian Cyst in 11 Girls


Clinical, Biological and Genetic Analysis of Prepubertal Isolated Ovarian Cyst in 11 Girls

Raja Brauner et al. PLoS One.


Background: The cause of isolated gonadotropin-independent precocious puberty (PP) with an ovarian cyst is unknown in the majority of cases. Here, we describe 11 new cases of peripheral PP and, based on phenotypes observed in mouse models, we tested the hypothesis that mutations in the GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX may be associated with this phenotype.

Methodology/principal findings: 11 girls with gonadotropin-independent PP were included in this study. Three girls were seen for a history of prenatal ovarian cyst, 6 girls for breast development, and 2 girls for vaginal bleeding. With one exception, all girls were seen before 8 years of age. In 8 cases, an ovarian cyst was detected, and in one case, suspected. One other case has polycystic ovaries, and the remaining case was referred for vaginal bleeding. Four patients had a familial history of ovarian anomalies and/or infertility. Mutations in the coding sequences of the candidate genes GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX were not observed.

Conclusions/significance: Ovarian PP shows markedly different clinical features from central PP. Our data suggest that mutations in the GNAS1, NR5A1, LHCGR, FSHR StAR, DMRT4 and NOBOX genes are not responsible for ovarian PP. Further research, including the identification of familial cases, is needed to understand the etiology of ovarian PP.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. Pedigrees of 4 cases with familial history of ovarian anomalies.
In case 2, the mother had an orange-sized ovarian cyst that was removed surgically in emergency at the age of 10 years. In case 5, four paternal aunts had vaginal bleeding and all were reported as infertile; in addition both the mother and maternal grandmother also reported menometrorragias. Hysterectomy was performed in the mother at 42 years because of a uterus fibroma diagnosed at 30 years. In case 9, the mother had an ovarian dermoid cyst at 25 years, leading to an ovariectomy; her mother's aunt was infertile, due to an undetermined ovarian trouble, after a menarche at the age of 10 years; her grand-mother's cousin underwent ovariectomy for an ovarian cyst. In case 10, the mother had ovarian cysts although there was no evidence of PP. Squares represent male family members, whilst circles represent female family members. The proband in each case is indicated by an arrow. Solid symbols indicate individuals with ovarian cysts. Shaded symbols indicate individuals with infertility and/or ovarian anomalies.

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