New insights into the genetic basis of premature ovarian insufficiency: Novel causative variants and candidate genes revealed by genomic sequencing.

Ovarian deficiency, including premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR), represents one of the main causes of female infertility. POI is a genetically heterogeneous condition but current understanding of its genetic basis is far from complete, with the cause remaining unknown in the majority of patients. The genes that regulate DOR have been reported but the genetic basis of DOR has not been explored in depth.

STAG3 homozygous missense variant causes primary ovarian insufficiency and male non-obstructive azoospermia.

Infertility, a global problem affecting up to 15% of couples, can have varied causes ranging from natural ageing to the pathological development or function of the reproductive organs. One form of female infertility is premature ovarian insufficiency (POI), affecting up to 1 in 100 women and characterised by amenorrhoea and elevated FSH before the age of 40. POI can have a genetic basis, with over 50 causative genes identified.

Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency.

Background: The term Pontocerebellar hypoplasias collectively refers to a group of rare, heterogeneous and progressive disorders, which are frequently inherited in an autosomal recessive manner and usually have a prenatal onset. Mutations in the SEPSECS gene, leading to deficiency in selenoprotein biosynthesis, have been identified in recent times as the molecular etiology of different pre/perinatal onset neurological phenotypes, including cerebello-cerebral atrophy, Pontocerebellar hypoplasia type 2D and progressive encephalopathy with elevated lactate. These disorders share a similar spectrum of central (e.

Severe sex differentiation disorder in a boy with a 3.8 Mb 10q25.3-q26.12 microdeletion encompassing EMX2.

The molecular basis of male disorders of sex development (DSD) remains unexplained in a large number of cases. EMX2 has been proposed to play a role in the masculinization process for the past two decades, but formal evidence for this causal role is scarce. The aim of this study is to yield additional support to this hypothesis by reporting on a male patient who presented with 46,XY DSD, a single kidney, intellectual disability, and the smallest microdeletion including EMX2 reported to date.