kallmann syndrome

exome sequencing

sex development

multiple endocrine neoplasia

novel mutation

pathogenic variants

sanger sequencing

autosomal recessive

missense mutation

mutation

Reproductive BioMedicine Online

<h2>Abstract</h2><h3>Research question</h3> Primary ovarian insufficiency (POI) is defined as the early exhaustion of ovarian function, before the age of 40 years. Its origin is genetic in 20–25% of cases. In rare cases, sequence variants of the <i>NR5A1</i>/SF-1 gene may result in POI, or in various disorders of gonadal development (DGD) or adrenal insufficiency. <h3>Design</h3> This study describes the cases of two families in which the association of DGD and POI enabled a diagnosis of <i>NR5A1</i> deleterious variations. Their clinical, hormonal, ultrasound and genetic characteristics are reported. <h3>Results</h3> The mothers of the affected children were 21 and 29 years when POI was diagnosed. Each nonetheless had two spontaneous pregnancies. The children have different phenotypes and different forms of DGD. None of the affected family members had adrenal insufficiency. A new sequence variant of the <i>NR5A1</i> gene was identified in one family: p.Cys283Phe (c.848G>T), and the <i>NR5A1</i> sequence variant c.86G>C was found in the other family. <h3>Conclusion</h3> Sequence variation of the <i>NR5A1</i> gene is a possibility that must be considered when a woman with POI or a diminished ovarian reserve has a family member or child with DGD. If a variant is identified, genetic counselling is essential for the patient and his/her family.

In cases of familial primary ovarian insufficiency and disorders of gonadal development, consider NR5A1/SF-1 sequence variants