NOBOX is an ovarian specific transcription factor that plays an important role in follicular growth and survival. Nineteen NOBOX variants have been previously associated with premature ovarian insufficiency (POI). Disease severity in patients with heterozygous and homozygous mutations largely overlap however, hampering genotype-phenotype correlations. We recently reported the first case of biallelic truncating mutations (NM_001080413.3 (NOBOX):c.826C>T, p.(Arg276*) and NM_001080413.3(NOBOX):c.1421del, p.(Gly474Alafs*76)) of NOBOX in two Belgian sisters with POI.

Pulmonary embolism (PE) is a blockage of blood flow in the pulmonary artery bed that can result in a life-threatening and potentially reversible right ventricular failure [1]. PE remains one of the leading causes of poor prognosis and death, particularly when a shock or right ventricular failure occurs [2]. According to studies, PE is generally manifested in a nonspecific manner

Atrial septal defect (ASD) is a common congenital heart disease diagnosed during childhood. Persistently increased pulmonary blood flow and dilated right atrium (RA) and right ventricle (RV) result in multiple symptoms and morbidities in adulthood; untreated adults may develop exercise intolerance, congestive heart failure, atrial tachyarrhythmias, pulmonary hypertension (PH), embolic stroke, or even death.

The main symptom in Chronic Obstructive Pulmonary Disease (COPD) is shortness of breath. Shortness of breath occurs especially with exercise and progresses over the years despite all medical treatments. One of the main mechanisms by which this symptom occurs is hyperinflation in the lungs [1].

Preterm premature rupture of membrane is the rupture of the chorionic-amniotic membrane and leakage of amniotic fluid before the onset of labor pains and prior to the 37^th week of pregnancy. Preterm premature rupture of membrane (PPROM) occurs in 3% of pregnancies and is the cause of about 25 to 30% of all preterm births. PPROM is an important contributor to perinatal morbidity.