Actualités - Aktuell

Protocol GenoDENT: Implementation of a New NGS Panel for Molecular Diagnosis of Genetic Disorders with Orodental Involvement.

2019/ Methods Mol Biol. 2019;1922:407-452.

 

Wehrle A, Witkos TM, Unger S, Schneider J, Follit JA, Hermann J, Welting T, Fano V, Hietala M, Vatanavicharn N, Schoner K, Spranger J, Schmidts M, Zabel B, Pazour GJ, Bloch-Zupan A, Nishimura G, Superti-Furga A, Lowe M, Lausch E.

 

Rare genetic disorders are often challenging to diagnose. Anomalies of tooth number, shape, size, mineralized tissue structure, eruption, and resorption may exist as isolated symptoms or diseases but are often part of the clinical synopsis of numerous syndromes (Bloch-Zupan A, Sedano H, Scully C. Dento/oro/craniofacial anomalies and genetics, 1st edn. Elsevier, Boston, MA, 2012). Concerning amelogenesis imperfecta (AI), for example, mutations in a number of genes have been reported to cause isolated AI, including AMELX, ENAM, KLK4, MMP20, FAM83H, WDR72, C4orf26, SLC24A4, and LAMB3. In addition, many other genes such as DLX3, CNNM4, ROGDI, FAM20A, STIM1, ORAI1, and LTBP3 have been shown to be involved in developmental syndromes with enamel defects. The clinical presentation of the enamel phenotype (hypoplastic, hypomineralized, hypomature, or a combination of severities) alone does not allow a reliable prediction of possible causative genetic mutations. Understanding the potential genetic cause(s) of rare diseases is critical for overall health management of affected patient. One effective strategy to reach a genetic diagnosis is to sequence a selected gene panel chosen for a determined range of phenotypes. Here we describe a laboratory protocol to set up a specific gene panel for orodental diseases.

Read the article: https://www.ncbi.nlm.nih.gov/pubmed/30838594

27 décembre 2019|Articles scientifiques|

Hypomorphic mutation of TRIP11 cause odontochondrodysplasia

2019/ JCI Insight. 2019 Feb 7;4(3).

 

Wehrle A, Witkos TM, Unger S, Schneider J, Follit JA, Hermann J, Welting T, Fano V, Hietala M, Vatanavicharn N, Schoner K, Spranger J, Schmidts M, Zabel B, Pazour GJ, Bloch-Zupan A, Nishimura G, Superti-Furga A, Lowe M, Lausch E.

 

Odontochondrodysplasia (ODCD) is an unresolved genetic disorder of skeletal and dental development. Here, we show that ODCD is caused by hypomorphic TRIP11 mutations, and we identify ODCD as the nonlethal counterpart to achondrogenesis 1A (ACG1A), the known null phenotype in humans. TRIP11 encodes Golgi-associated microtubule-binding protein 210 (GMAP-210), an essential tether protein of the Golgi apparatus that physically interacts with intraflagellar transport 20 (IFT20), a component of the ciliary intraflagellar transport complex B. This association and extraskeletal disease manifestations in ODCD point to a cilium-dependent pathogenesis. However, our functional studies in patient-derived primary cells clearly support a Golgi-based disease mechanism. In spite of reduced abundance, residual GMAP variants maintain partial Golgi integrity, normal global protein secretion, and subcellular distribution of IFT20 in ODCD. These functions are lost when GMAP-210 is completely abrogated in ACG1A. However, a similar defect in chondrocyte maturation is observed in both disorders, which produces a cellular achondrogenesis phenotype of different severity, ensuing from aberrant glycan processing and impaired extracellular matrix proteoglycan secretion by the Golgi apparatus.

Read the article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413787/

27 décembre 2019|Articles scientifiques|

Application RARENET/GeniDENT

logo_GeniDENT

Développée  pour les patients du projet RARENET/INTERREG V, l’application RARENET/GeniDENT offre la possibilité de renseigner des questionnaires portant sur la santé, les traitements et la qualité de vie. Compilées et étudiées par les chercheurs, les professionnels de santé, ces données – anonymisées et sécurisées – sont utiles pour attirer l’attention sur des aspects mal connus et peu documentés, comme l’importance des problèmes de la bouche et des dents en association avec d’autres signes dans les maladies rares.

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27 décembre 2019|Evénements|

Dental Findings in Patients With Non-surgical Hypoparathyroidism and Pseudohypoparathyroidism: A Systematic Review

2018 / English Frontiers in Physiology. 2018 Jun 19;9:701.

 

Hejlesen J, Underbjerg L, Gjørup H, Bloch-Zupan A, Sikjaer T, Rejnmark L, Haubek D.

 

Background: Dental aberrations have been mentioned in relation to non-surgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP). However, a systematic review of dental characteristics have not been performed. The present systematic review describes the dental findings in patients with Ns-HypoPT and PHP.

Methods: Studies on Ns-HypoPT and PHP reporting dental features were eligible. A systematic literature search was conducted using four bibliographic databases (Web of Science, Scopus, Pubmed, and Embase) and was limited to studies written in English. Reviews, meta-analyses and letters were excluded. Both the research and reporting of results were based on PRISMA (preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines.

Results: Of 88 studies included, nine were cross-sectional, one was a prospective cohort study, 26 were case series, and 52 were case reports. The most frequently reported findings in patients with Ns-HypoPT were enamel opacities, enamel hypoplasia, hypodontia, and eruption disturbances. In patients with PHP, enamel hypoplasia, eruption disturbance, and deviation of the root morphology were the most frequently reported findings.

Conclusion: An association between enamel hypoplasia and Ns-HypoPT and PHP is likely. The results should, however, be interpreted cautiously due to the limited number of high-quality studies. The present review confirms the need of further well-designed studies, such as large-scale studies, e.g., multicenter studies, to conclude on the reported associations between Ns-HypoPT/PHP and enamel hypoplasia.

Read the article: https://www.frontiersin.org/articles/10.3389/fphys.2018.00701/full

6 novembre 2019|Articles scientifiques|

Genetic Evidence Supporting the Role of the Calcium Channel, CACNA1S, in Tooth Cusp and Root Patterning

2018 / English – Frontiers in Physiology, 26 September 2018, 9:1329.

 

Laugel-Haushalter V, Morkmued S, Stoezel C, Geoffroy V, Muller J, Boland A, Deleuze J-F, Chennen K, Pitiphat W, Dolflus H, Niederreither K, Bloch-Zupan A,  Pungchanchaikul P.

 

“In this study, we report a unique dominantly inherited disorganized supernumerary cusp and single root phenotype presented by 11 affected individuals belonging to 5 north-eastern Thai families. Using whole exome sequencing (WES) we identified a common single missense mutation that segregates with the phenotype in exon 6 of CACNA1S (Cav1.1) (NM_000069.2: c.[865A > G];[=] p.[Ile289Val];[=]), the Calcium Channel, Voltage-Dependent, L Type, Alpha-1s Subunit, OMIM 114208), affecting a highly conserved amino-acid isoleucine residue within the pore forming subdomain of CACNA1S protein. This is a strong genetic evidence that a voltage-dependent calcium ion channel is likely to play a role in influencing tooth morphogenesis and patterning.”

Read the article: https://www.frontiersin.org/articles/10.3389/fphys.2018.01329/full

6 novembre 2019|Articles scientifiques|

Web-Emission « Intelligence artificielle et maladies rares » de la Fondation Maladies Rares

Comment utiliser l’intelligence artificielle afin de mieux diagnostiquer les maladies rares ? Diffusé en direct le 11 septembre 2019, revoyez  cette vidéo avec Prof. Bloch-Zupan du projet RARENET.

19 septembre 2019|Evénements|

Les doctorants de RARENET

Nous avions l’honneur d’assister deux doctorants pendant leurs études et leurs recherches dans le cadre du projet RARENET.

Philippe KAYASSEH a soutenu sa thèse sur Les Syndromes d’Ehlers-Danlos et leur prise en charge bucco-dentaire le 10 mai 2019.

Liora BELASSEIN-WOLFF a soutenu sa thèse une Etude sur la prévalence des maladies rares à expressions bucco-dentaires sur une population d’enfants de la maternelle au CM2 de la Ville de Strasbourg le 01 juillet 2019.

Toutes nos félicitations aux nouveaux diplômés de docteur et un grand merci pour vos contributions !

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13 août 2019|Evénements|

Retour au Webinar sur les amémogenèses imparfaites

Notre Webinar sur les amélogenèses imparfaites était un succès !  Si vous avez manqué cette occasion ou si vous voulez voir le replay en ligne, rendez-vous sur YouTube!

 

Retrouvez les informations en forme écrite sur :
https://www.dentalespace.com/praticien/actualites/amelogeneses-imparfaites-a-z/

 

24 juillet 2019|Evénements|

RARENET et l’European Society of Human Genetics

18 juin 2018, à Milan, Italie.  Lors de l’European Human Genetics Conference annuelle, Pr. Agnès Bloch-Zupan de RARENET a donné une présentation sur GenoDENT.  Cliquez au-dessous pour voir la vidéo sur YouTube (en anglais).

 

24 juillet 2019|Evénements|

RARENET recherche un prestataire

Consultation prestataire développement webapp

 

Dans le cadre du projet RARENET – INTERREG :
Un réseau trinational pour l’enseignement, l’étude et la prise en charge de maladies complexes et rares dans le Rhin supérieur

nous recherchons …

un prestataire afin de mettre en place une webapp.

  • Compétences demandées :
    • —Graphisme et ergonomie
    • —Bonnes connaissance du secteur des maladie rares
    • —Programmation informatique langage Python / Django. Capacité notamment à corriger et améliorer du code déjà écrit.
    • —Bonne maîtrise des langues : français / anglais / allemand

 

12 juillet 2019|Equipe|