Mutations in RELT cause autosomal recessive amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a collection of isolated (non-syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that perfectly segregated with homozygous defects in a novel gene: RELT that is a member of the tumor necrosis factor receptor superfamily (TNFRSF). RNAscope in situ hybridization of wild-type mouse molars and incisors showed specific Relt mRNA expression by secretory stage ameloblasts and by odontoblasts. Relt-/- mice generated by CRISPR/Cas9 exhibited incisor and molar enamel malformations. Relt-/- enamel had a rough surface and underwent rapid attrition. Normally unmineralized spaces in the deep enamel near the dentino-enamel junction (DEJ) were as highly mineralized as the adjacent enamel, which likely altered the mechanical properties of the DEJ. Phylogenetic analyses showed the existence of selective pressure on RELT gene outside of tooth development, indicating that the human condition may be syndromic, which possibly explains the history of small stature and severe childhood infections in two of the probands. Knowing a TNFRSF member is critical during the secretory stage of enamel formation advances our understanding of amelogenesis and improves our ability to diagnose human conditions featuring enamel malformations.

The effects of daily irradiation with polychromatic visible polarized light on human lymphocyte populations.

OBJECTIVE: The goal of this randomized, placebo controlled, double-blind study was to investigate the effects of transcutaneous irradiation with polychromatic visible polarized light (540-780 nm; 68% polarization; power density 3.0 E-10 W/cm(2)) on a subset population of human lymphocytes using flow cytometry. BACKGROUND DATA: The biomodulation and therapeutic effects of visible light of different wavelengths are well known, but the immunological effects of polychromatic visible polarized light have not been investigated sufficiently. METHODS: Before and after 28 consecutive days of irradiation, blood samples were collected from the subjects and the population count of the lymphocyte subset was measured. RESULTS: The absolute count of total lymphocytes, CD3(+) lymphocytes, and CD3(+)CD4(+) lymphocytes increased by 7% (p = 0.023), 9% (p = 0.058), and 13% (p = 0.021), respectively. Yet the absolute count of WBCs, CD3(+)CD8(+), CD19(+), and CD16(+)56(+) lymphocytes did not change significantly. CONCLUSION: The application of polychromatic visible polarized light with the aforementioned features increases the CD3(+)CD4(+) lymphocyte population. It is suggested that this regimen may be useful for the promotion of natural defenses in cell-mediated immunity.