PHEX Gene Mutations and Genotype-Phenotype Analysis of Korean Patients with Hypophosphatemic Rickets

X-linked hypophosphatemic rickets (XLH) results from mutations in the PHEX gene. Mutational analysis of the PHEX gene in 15 unrelated Korean patients with hypophosphatemic rickets revealed eight mutations, including five novel mutations, in nine patients: two nonsense mutations, two missense mutations, one insertion, and three splicing acceptor/donor site mutations. Of these, c.64G>T, c.1699C>T, c.466_467 insAC, c.1174-1G>A, and c.1768+5G>A were novel mutations. To analyze the correlation between genotype and phenotype, phenotypes were compared between groups with and without a mutation, in terms of mutation location, mutation type, and sex. Skeletal disease tended to be more severe in the group with a mutation in the C-terminal half of the PHEX gene, but no genotype-phenotype correlation was detected in other comparisons. Further extensive studies of the PHEX gene mutations and analyses of the genotype-phenotype relationships are required to understand PHEX function and the pathogenesis of XLH

Stephen F Austin State University Journal of Education Vol. 2 No. 1

https://scholarworks.sfasu.edu/edjournal/1001/thumbnail.jp

Microbial neuraminidase induces a moderate and transient myelin vacuolation independent of complement system activation

Aims: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. Methods: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles. Neuronal death in the affected axonal tracts was assessed by Fluoro-Jade B and anti-caspase-3 staining. To evaluate the role of the complement, membrane attack complex (MAC) deposition on damaged bundles was analyzed using anti-C5b9. Rats ICV injected with the anaphylatoxin C5a were studied for myelin damage. In addition, NA-induced vacuolation was studied in rats with different degrees of complement inhibition: normal rats treated with anti-C5-blocking antibody and C6-deficient rats. Results: The stria medullaris, the optic chiasm, and the fimbria were the most consistently damaged axonal tracts. Vacuolation peaked 7 days after NA injection and reverted by day 15. Olig2+ cell number in the damaged tracts was unaltered, and neurodegeneration associated with myelin alterations was not detected. MAC was absent on damaged axonal tracts, as revealed by C5b9 immunostaining. Rats ICV injected with the anaphylatoxin C5a displayed no myelin injury. When the complement system was experimentally or constitutively inhibited, NA-induced myelin vacuolation was similar to that observed in normal rats. Conclusion: Microbial NA induces a moderate and transient myelin vacuolation that is not caused either by neuroinflammation or complement system activation