Dysgerminoma Probably Due to a Novel SOHLH1-pathogenic Variant Causing Familial Ovarian Dysgenesis.

Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development.

Drug-resistant epilepsy: From multiple hypotheses to an integral explanation using preclinical resources.

Drug-resistant epilepsy affects approximately one-third of the patients with epilepsy. The pharmacoresistant condition in epilepsy is mainly explained by six hypotheses. In addition, several experimental models have been used to understand the mechanisms involved in pharmacoresistant epilepsy and to identify novel therapies to control this condition. However, the global prevalence of this disease persists without changes. Several factors can explain this situation. First of all, the pharmacoresistant epilepsy is explained by different and independent hypotheses. Each hypothesis indicates specific mechanisms to explain the drug-resistant condition in epilepsy. However, there are different findings suggesting common mechanisms between the different hypotheses. Other important situation is that the experimental models designed for the screening of drugs with potential anticonvulsant effect do not consider factors such as age, gender, type of epilepsy, and comorbid disorders. The present review focuses on indicating the limitations for each hypothesis and the relationships among them. The relevance to consider central and peripheral phenomena associated with the drug-resistant condition in different types of epilepsy is also indicated. The necessity to establish a global hypothesis that integrates all the phenomena associated with the pharmacoresistant epilepsy is proposed. This article is part of the Special Issue "NEWroscience 2018".