Mutations in the Latent TGF-beta Binding Protein 3 (LTBP3) Gene cause Brachyolmia with Amelogenesis Imperfecta

2015 / ENGLISH

M. Huckert, C. Stoetzel, S. Morkmued, V. Laugel-Haushalter, V. Geoffroy, J. Muller, F. Clauss, M. K. Prasad, F. Obry; J.L. Raymond, M. Switala, Y. Alembik, S. Soskin, E. Mathieu, J. Hemmerle, J.-L. Weickert, B. Dabovic, D. B. Rifkin, A. Dheedene, E. Boudin, O. Caluseriu, M.-C. Cholette, R. McLeod, R. Antequera, M.-P. Gelle, J.-L. Coeuriot, L.-F. Jacquelin, I.Bailleul-Forestier, M.-C. Maniere, W. Van Hul, D. Bertola, P.Dolle, A. Verloes, G. Mortier, H. Dollfus, A. Bloch-Zupan

Human Molecular Genetics 2015. doi: 10.1093/hmg/ddv053

12 February 2015|Scientific articles|

Genetic Alterations: Heritable Dentin Defects

2014 / ENGLISH

Bloch-Zupan A, “Genetics Alterations: Heritable Dentin Defects” in Goldberg M. (ed.), The Dental Pulp, DOI 10.1007/978-3-642-55160-4_11, Springer-Verlag Berlin Heidelberg 2014, p.155-168.

“Dentin defects that accompany rare genetic diseases[1,2] (diseases, that by definition affect less than 1/2,000 individuals) can be described phenotypically by various types of anomalies that not only impait the formation and structure of the dentin and per se the color of the teeth but also cause anormales of the crown, root, and/or pulp space shape and aberrantdentin formation such as pulpolithes or intrapulpal calcifications”

12 February 2015|Scientific articles|

A Novel Mutation in the ROGDI Gene in a Patient with Kohlschütter-Tönz Syndrome.

2014 / ENGLISH

Huckert M, Mecili H, Laugel-Haushalter V, Stoetzel C, Muller J, Flori E, Laugel V, Manière MC, Dollfus H, Bloch-Zupan A.
Mol Syndromol. 2014 Dec;5(6):293-8. doi: 10.1159/000366252. Epub 2014 Sep 11.

“Kohlschütter-Tönz Syndrome (KTZS) is an autosomal recessive disorder caused by mutations in the ROGDI gene. This syndrome is characterized by epilepsy, psychomotor regression and amelogenesis imperfecta. In this paper, we report a case of a 13-year-old Malian girl presenting with this rare disease. By genetic analysis, we identified a novel ROGDI homozygous mutation NM_024589.1: c.117+1G>T [Chr16 (GRCh37): g.4852382C>A] which confirmed the diagnosis of Kohlschütter-Tönz syndrome. The mutation abolishes the usual splice donor site of intron 2 which leads to the deletion of exon 2 and in-frame assembly of exon 3. Exon 2 encodes a highly conserved leucine-rich region that is essential for ROGDI protein function. Hence, this deletion may affect the function of the ROGDI protein.”

16 January 2015|Scientific articles|

Season’s greetings

carte_voeux_2014The INTERREG/OS “Oro-dental manifestations of rare diseases” project coordination thanks you deeply for your support and contribution in 2014.
We wish you great holidays and look forward to seeing you in 2015 for new challenges!
Keep smiling and see you soon in the Upper Rhine Valley!

Pr. Agnès Bloch-Zupan
Scientific coordinator

16 December 2014|Events|

Characterization of the first intragenic SATB2 duplication in a girl with intellectual disability, nearly absent speech and suspected hypodontia

2014 / ENGLISH

A.S. Kaiser, B. Maas, A. Wolff, C. Sutter, J.W.G. Janssen, K. Hinderhofer, U. Moog.
European Journal of Human Genetics, 13 August 2014; doi:10.1038/ejhg.2014.163.

“SATB2, a gene encoding a highly conserved DNA-binding protein, is known to have an important role in craniofacial and neuronal development. Only a few patients with SATB2 variants have been described so far. Recently, Döcker et al provided a summary of these patients and delineated the SAS (SATB2-associated syndrome). We here report on a girl with itellectual disability, nearly absent speech and suspected hypodontia who has shown to carry an intragenic SATB2 tandem duplication hypothesized to lead to haploinsufficiency of SATB2. Preliminary information on this patient had already benn included in the article by Döcker et al. We want to give a detailed description of the patient’s phenotype and genotype, providing further insight into the spectrum of the molecular mechanisms leading to SAS. (…)”

28 November 2014|Scientific articles|

Anomalien der Zähne, des Gesichtes und des Schädels – genetische Grundlagen und Gegenwärtige Forschung

2014 / DEUTSCH

S. Feierabend.
Oralprophylaxe Kinderzahnheilkd 2014;36:26-31
DOI 10.3238/OPKZH.2014.0026-0031

“Während in der Humanmedizin die Entdeckung genetischer Grundlagen verschiedener Erkrankungen zum medizinischen Alltag gehört, gewinnt dies in der Zahnmedizin erst langsam an Bedeutung. Insbesondere bei Patienten mit Seltenen Erkrankungen kann oft erst die Genetik Aufschluss über die Krankheitsursache geben. (…)”

28 November 2014|Scientific articles|

Behandlungskonzepte bei Strukturanomalien des Zahnschmelzes und des Dentins

2014 / DEUTSCH
S. Feierabend.
wissen kompakt 2014. 8:13-25 DOI 10.1007/s11838-013-0193-8, 23. Januar 2014

“Die verschiedenen Strukturanomalien der Zähne sind in ihrer Summe verhältnismässig häufig in der zahnärztlichen Praxis anzutreffen. Die wissenschaftliche Grundlage zur Behandlung dieser Erkrankungen steht dagegen auf keiner breitgefâcherten Basis, da die einzelne Erkrankung wiederum zu selten vorkommt, um Studien mit hohem Evidenzniveau durchführen zu können. Für die zahnärztliche Therapie dieser Zahnveränderungen ist es essenziell, die richtige Diagnose zu stellen, um das Verfahren mit der günstigten Prognose anwenden und so auch das entsprechende Material auswählen zu können. (…)”

28 November 2014|Scientific articles|

RSK2 Is a Modulator of Craniofacial Development

2014 / ENGLISH

V. Laugel-Haushalter, M. Paschaki, P. Marangoni, C. Pilgram, A. Langer, T. Kuntz, J. Demassure, S. Morkmued, P. Choquet, A. Constantinesco, F. Bornert, M. Schmittbuhl, S. Pannetier, L. Viriot, A. Hanauer, P. Dollé, A. Bloch-Zupan. (2014).
PloS ONE 9(1):e84343. Doi:10.1371/journal.pone.0084343

“The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized. (…)”

28 November 2014|Scientific articles|

Homozygous and Compound Heterozygous MMP20 Mutations in Amelogenesis Imperfecta

2013 / ENGLISH

B. Gasse, E. Karayigit, E. Mathieu, S. Jung, A. Garret, M. Huckert, S. Morkmued, C. Schneider, L. Vidal, J. Hemmerlé, J.-Y. Sire, A. Bloch-Zupan.
Journal of Dental Research, 2013.

“In this article, we focus on hypomaturation autosomal-recessive-type amelogenesis imperfecta (type IIA2) and describe 2 new casual Matrix metalloproteinase 20 (MMP20) mutations validated in two unrelated families: a missense mutation p.T130I at the expected homozygous state, and a compound heterozygous mutation having the same mutation combined with a nucleotide deletion, leading to a premature stop cordon (p.N120fz*2). (…)”

27 November 2014|Scientific articles|

Molars and incisors: show your microarray IDs

2013 / ENGLISH

V. Laugel-Haushalter, M. Paschaki, C. Thibault-Carpentier, D. Dembelé, P. Dollé, A. Bloch-Zupan.
BMC Research Notes 2013, 6 : 113.

“One of the key questions in developmental biology is how, from a relatively small number of conserved signalling pathways, is it possible to gnerate organs displaying a wide range of shapes, tissue organization, and function. The dentition and its dinstinct specific tooth types represent a valuable system to address the issues of differential molecular signatures. (…)”

27 November 2014|Scientific articles|

Aspects législatifs des maladies rares : conseil génétique, éthique, relation praticien-patient


P. Levigne, C. Cordier, A. Bloch-Zupan.
Revue d’ODF, Revue Orthopédique Dento faciale 2013 ; 47 : 421-431.

“Le développement de la médecine bucco-dentaire prédictive est porteuse de beaucoup d’espoirs mais des dérives sont toujours possibles. Les tests génétiques étant en première ligne de cette médecine prédictive, une législation a été établie encadrant l’activité relative à la génétique à la fois ouverte sur les avancées que pevent apporter ces tests génétiques et, en même temps, respectueuse des droits fondamentaux des patients et plus particulièrement des mineurs. (…)”

27 November 2014|Scientific articles|

Evidence-based Dentistry – Tipps für die Praxis. Fall 7: Seltene Erkrankungen – relevant für den Zahnarzt?

2013 / DEUTSCH

S. Feierabend, E. Hellwig, O. Frei, A. Petersen, E. Lausch, A. Wolff, U.Moog, H. Dollfus, C. Stoetzel, M. Huckert, M.-C. Manière, S. Troester, F. Clauss, A. Bloch-Zupan, S. Gerhardt-Szép.
Deutscher Ärzte-Verlag, Deutsche Zahnärztliche Zeitschrift, 2013; 67 (1).

“Liebe Kolleginnen und Kollegen, dieser Beitrag wird in seiner äusseren Form etwas von den bisherigen abweichen. Grund dafür ist das Thema: “Seltene Erkrankungen. (…)”

27 November 2014|Scientific articles|

Science Days 2014: the teeth from all sides

16-18 October 2014 – Europa Park – Rust (Germany)

LogoSD14_oURLThe INTERREG/Offensive Science project “Oro-dental manifestations of rare diseases” will participate from October 16th until October 18th 2014 in the Science Days organised by the Förderverein Science & Technologie e.V. in Europa-Park in Rust (Germany).

18 000 visitors participated in the event in 2013. The audience of the scientific and educational activities is composed of pupils (children and adolescents) as well as teachers and families.

Between the 90 stands present during this event, the cross-border research project will propose several activities on the topic “the teeth from all sides”.

The aim of these workshops is to make the visitors aware of the project problematic and the role of the EU in supporting research.

The scientific mediation activities will be animated by project members and students that will enable the visitors to revise their general knowledge of the teeth through playful and interactive activities.

Indeed, the visitors will be asked to recognise the different kinds of teeth as well as to find out the age of a patient with the aid of radiographs. Moreover, they will discover the variability of the gene responsible for dentition through a compared anatomy workshop. They will also discover oral abnormalities as a manifestation of rare diseases.

More information on the Science days and the Förderverein Science & Technologie e.V.:

The “Genosmile”-animation is also registered in the framework of the Dialog Science of the Trinational Metropolitan region upper Rhine.Logo Dialog Science RMTMO

More information on the Dialog Science:


19 September 2014|Events|

Cooperation with Strasbourg University students

As part of their Master’s degree in Science Communication, students at Strasbourg University are basing their supervised project on the subject of Rare Diseases and their oro-dental manifestations. They will be studying the communication on rare diseases in Europe to identify which are the most suitable messages and aids for understanding such diseases, their oro-dental manifestations, their effects and treatments and to take a closer look at the work of researchers and to encourage interested parties to consult a reference centre.

4 March 2014|Project|

7th Human and Clinical Genetics Congress

29, 30 & 31 January 2014, Bordeaux
The Human and Clinical Genetic Congress is the venue for all those involved in the field to meet up every two years in a major French city. The conferences welcome over 1,400 participants, partner representatives and exhibitors as well as nearly twenty local and national associations that regularly attend the event.
The partners of our project will be at the conference to share the results of their research via an oral presentation on the RSK2 gene (a modulator of craniofacial development) and during the poster session on the subject of‘monogenic diseases: from the clinic to the mechanism’.
Presentations and posters’ abstracts can be consulted in the compendium available on the congress website: (pdf)

4 March 2014|Events|

A possible cranio-oro-facial phenotype in Cockayne syndrome

2013 / ENGLISH
Agnès Bloch-Zupan, Morgan Rousseaux, Virginie Laugel, Matthieu Schmittbuhl, Rémy Mathis, Emmanuelle Desforges, Mériam Koob, Ariane Zaloszyc, Hélène Dollfus and Vincent Laugel

Cockayne Syndrome CS is a rare autosomal recessive neurological disease caused by defects in DNA repair characterized by progressive cachectic dwarfism, progressive intellectual disability with cerebral leukodystrophy, microcephaly, progressive pigmentary retinopathy, sensorineural deafness photosensitivity and possibly orofacial and dental anomalies. […]

4 March 2014|Scientific articles|

From the Transcription of Genes Involved in Ectodermal Dysplasias to the Understanding of Associated Dental Anomalies

2012 – August / ENGLISH
V. Laugel-Haushalter, A. Langer, J. Marrie, V. Fraulob, B. Schuhbaur, M. Koch-Phillips, P. Dollé, A. Bloch-Zupan

Orodental anomalies are one aspect of rare diseases and are increasingly identified as diagnostic and predictive traits. To understand the rationale behind gene expression during tooth or other ectodermal derivative development and the disruption of odontogenesis or hair and salivary gland formation in human syndromes we analyzed the expression patterns of a set of genes (Irf6, Nfkbia, Ercc3, Evc2, Map2k1) involved in human ectodermal dysplasias in mouse by in situ hybridization. […]

4 February 2012|Scientific articles|

Homozygosity Mapping and Candidate Prioritization Identify Mutations, Missed by Whole-Exome Sequencing, in SMOC2, Causing Major Dental Developmental Defects

2011 – December / ENGLISH
Agnès Bloch-Zupan, Xavier Jamet, Christelle Etard, Virginie Laugel, Jean Muller, Véronique Geoffroy, Jean-Pierre Strauss, Valérie Pelletier, Vincent Marion, Olivier Poch, Uwe Strahle, Corinne Stoetzel, and Helène Dollfus.

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. Homozygosity mapping revealed a unique zone on 6q27-ter. […]

4 December 2011|Scientific articles|

Clinical utility gene card for: hypophosphatasia

2011 / ENGLISH
Etienne Mornet, Christine Beck, Agnès Bloch-Zupan, Hermann Girschick and Martine Le Merrer

4 February 2011|Scientific articles|

Les amélogenèses imparfaites

2010 – Octobre / FRANÇAIS
Agnès Bloch-Zupan

Parmi les anomalies dentaires, l’amélogenèse imparfaite est, dans certaines de ses formes, l’une des plus sévères et des plus difficiles à prendre en charge sur le plan esthétique et fonctionnel. […]

4 October 2010|Scientific articles|