Maturation of the vertebral ring apophysis is delayed in girls with adolescent idiopathic scoliosis compared to the normal population.

PURPOSE: The ring apophysis is a secondary ossification center on both sides of each vertebral body, to which the annulus of the intervertebral disc inserts. Recently, its pattern of ossification and fusion to the vertebral body was described for the normal growing spine. The aim of the present study was to investigate the ossification and fusion of the ring apophysis in patients with adolescent idiopathic scoliosis (AIS) and compare it to the normal growing population. METHODS: Ring apophysis maturation along the entire thoracic and lumbar spine was analyzed on CT scans of 99 female, pre-operative AIS patients and compared to 134 CT scans of non-scoliotic girls, aged 12 to 20. RESULTS: The ring apophysis maturation in AIS patients was delayed at all spinal levels in AIS patients compared to non-scoliotic controls. Ossification starts at T4-T11 at age 12, followed by T1-T5 and L3-S1 at age 15. The fusion process in AIS patients continues longer in the midthoracic region as compared to the other regions and as compared to non-scoliotic controls, with many incomplete fusions still at age 20. CONCLUSION: The ring apophysis maturation in AIS is delayed compared to that in the normal population and lasts longer in the mid/low thoracic spine. Delayed maturation of the spine's most important stabilizer, while the body's dimensions continue to increase, could be part of the patho-mechanism of AIS.

Linking genotype to trophoblast phenotype in preeclampsia and HELLP syndrome associated with STOX1 genetic variants.

Preeclampsia is a major hypertensive pregnancy disorder with a 50% heritability. The first identified gene involved in the disease is STOX1, a transcription factor, whose variant Y153H predisposes to the disease. Two rare mutations were also identified in Colombian women affected by the hemolysis, elevated liver enzyme, low platelet syndrome, a complication of preeclampsia (T188N and R364X). Here, we explore the effects of these variants in trophoblast cell models (BeWo) where STOX1 was previously invalidated. We firstly showed that STOX1 knockout alters response to oxidative stress, cell proliferation, and fusion capacity. Then, we showed that mutant versions of STOX1 trigger alterations in gene profiles, growth, fusion, and oxidative stress management. The results also reveal alterations of the STOX interaction with DNA when the mutations affected the DNA-binding domain of STOX1 (Y153H and T188N). We also reveal here that a major contributor of these effects appears to be the E2F3 transcription factor.