Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene.

Four individuals from two families presented with a multisystemic condition of suspected genetic origin that was diagnosed only after genome analysis. The main phenotypic features were immune system dysregulation (severe immunodeficiency with autoimmunity) and intellectual disability. The four individuals were found to be homozygous for a 4.4 Kb deletion removing exons 20-23 (NM_003291.4) of the TPP2 gene, predicting a frameshift with premature termination of the protein. The deletion was located on a shared chromosome 13 haplotype indicating a Swiss founder mutation. Tripeptidyl peptidase 2 (TPP2) is a protease involved in HLA/antigen complex processing and amino acid homeostasis. Biallelic variants in TPP2 have been described in 10 individuals with variable features including immune deficiency, autoimmune cytopenias, and intellectual disability or chronic sterile brain inflammation mimicking multiple sclerosis. Our observations further delineate this severe condition not yet included in the OMIM catalog. Timely recognition of TPP2 deficiency is crucial since (1) immune surveillance is needed and hematopoietic stem cell transplantation may be necessary, and (2) for provision of genetic counselling. Additionally, enzyme replacement therapy, as already established for TPP1 deficiency, might be an option in the future.

[The teeth shape. An essential element of the diagnosis]. / La forme des dents. Un élément incontournable du diagnostic.

Form is often linked to function. This applies particularly to teeth; the phylogenesis of our dentition shows that the dental formula was established long before Homo sapiens. Today, the shape of teeth has several roles: chewing, aesthetics and periodontal balance. The analysis of the literature shows the importance of shapes, particularly in the periodontal equilibrium. Diagnostic analysis of the shapes enables us to detect those that are said to be at risk and to prevent iatrogenic effects due to dental alignment. By applying this shape analysis to clinical examples, we will show the interest of this approach in the treatment of dental-maxillary disharmony, in the prevention of the loss of papillae associated with the opening of black triangles and the aesthetic improvement of shapes. The characterization of tooth shapes is an essential diagnostic element for a safer and more harmonious orthodontic treatment.

Tripeptidyl-peptidase II: Update on an oldie that still counts.

The huge exopeptidase, tripeptidyl-peptidase II (TPP II), appears to be involved in a large number of important biological processes. It is present in the cytosol of most eukaryotic cells, where it removes tripeptides from free amino termini of longer peptides through a 'molecular ruler mechanism'. Its main role appears to be general protein degradation, together with the proteasome. The activity is increased by stress, such as during starvation and muscle wasting, and in tumour cells. Overexpression of TPP II leads to accelerated cell growth, genetic instability and resistance to apoptosis, whereas inhibition or down-regulation of TPP II renders cells sensitive to apoptosis. Although it seems that humans can survive without TPP II, it is not without consequences. Recently, patients with loss-of-function mutations in the TPP2 gene have been identified. They suffer from autoimmunity leading to leukopenia and other consequences. Furthermore, a missense mutation in the TPP2 gene is associated with a sterile brain inflammation condition mimicking multiple sclerosis. This review will summarise what is known today regarding the activity and structure of this very large enzyme complex, and its potential function in various cellular processes. It is clear that more research is needed to identify natural substrates and/or interaction partners of TPP II, which can explain the observed effects in different cellular contexts.

Black triangle dilemma and its management in esthetic dentistry.

In recent years, clinician and dentist's esthetic demand in dentistry have increased rapidly, driven by an enhanced awareness of beauty and esthetics. The ultimate goal in modern restorative dentistry is to achieve "white" and "pink" esthetics in esthetically important zones. "White esthetics" is the natural dentition or the restoration of dental hard tissues with suitable materials. "Pink esthetics" refers to the surrounding soft-tissues, which includes the interdental papilla and gingiva that can enhance or diminish the esthetic result. Reconstruction of the lost interdental papilla is one of the most challenging and least predictable problems. Restoration and maintenance of these tissues with adequate surgical and prosthetic techniques are a real challenge in modern esthetic dentistry. Treatment of marginal tissue recession, excessive gingival display, deficient ridges, ridge collapse, and esthetic defects around teeth and implants are some of the esthetic problems associated with the interdental papilla that have to be corrected in todays scenario which has been discussed in this review.