No abstract

Coronavirus disease is an infectious disease caused by a new virus which causes respiratory illness. Older adults and people who have previous chronic medical conditions are at higher risk for more serious complications from COVID-19. Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, Cardiovascular event and associated comorbidities, which are the main causes of severe clinical problem in COVID-19 patients. Considering the protective role of vitamin D through modulating the innate and adaptive immune system as well as inhibition of Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.

Coronavirus disease (COVID-19) is an infectious disease caused by a new virus which causes respiratory illness. Older adults and people who have previous chronic medical conditions are at higher risk for more serious complications from COVID-19.Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, Cardiovascular event and associated comorbidities, which are the main causes of severe clinical problem in COVID-19 patients. Considering the protective role of vitamin D through modulating the innate and adaptive immune system as well as inhibition of Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.

PPFIBP1 encodes for the liprin-β1 protein which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 14 individuals from 10 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy and progressive microcephaly. Further common clinical findings included muscular hypertonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired hearing and vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM-domain region that is essential for protein-protein interaction. For further insight in the effects of PPFIBP1 loss-of-function, we performed automated behavioural phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model which revealed defects in spontaneous and light-induced behaviour and confirmed resistance to the acetylcholinesterase inhibitor aldicarb suggesting a defect in the neuronal presynaptic zone. In conclusion, we present bi-allelic loss-of-function variants in PPFIBP1 as a novel cause of an autosomal recessive neurodevelopmental disorder.