Inflammation in atherosclerosis: Drivers, mechanisms and therapies.

A systematic literature review was performed by searching Web of Science and PubMed using the following terms: (“ZBTB20”) AND (“Kallmann syndrome” OR “congenital hypogonadotropic hypogonadism” OR “GnRH deficiency”), with no language restrictions. Accumulating work has uncovered critical developmental events relevant to CHH pathogenesis, yet many genetic contributors remain to be discovered. The terminal nerve (TN) is thought to serve as a migratory scaffold for GnRH neurons. Olfactory bulb (OB) malformations are frequently observed in patients with CHH with anosmia/hyposmia, i.e., Kallmann syndrome (KS). Nevertheless, severe OB hypoplasia does not invariably lead to reproductive phenotypes, and the link between GnRH deficiency and OB atrophy in KS remains unclear. We identify as a CHH-associated gene through a pathogenic variant (p.R300C) that fully segregates in a large four-generation family, with further support from a significant enrichment of rare variants in our CHH cohort (n = 812). Nervous system-specific knockout mice recapitulate core CHH features, including GnRH neuron deficiency, hypogonadism, and infertility. deficiency disrupts the TN scaffold, which likely underlies the arrested migration of GnRH neurons. Moreover, loss impairs the proliferation of neural stem cells in the subventricular zone (SVZ) and disrupts neuroblast migration along the rostral migratory stream. We also identify as a direct transcriptional target of ZBTB20, revealing the ZBTB20-Thbs4 axis as a key regulatory pathway in SVZ-OB neurogenesis.