Amelogenesis Imperfecta

Clinical and Molecular Study of Amelogenesis Imperfecta

Amelogenesis Imperfecta (AI) are a heterogeneous group of rare genetic diseases transmitted according to various mode of inheritance (X-linked, autosomal dominant, autosomal recessive) affecting the formation/mineralization of tooth enamel. These diseases exist in isolation with clinical manifestations limited to the oral cavity or may be associated to other symptoms in syndromes. Many different genes (AMELX, ENAM, ENAMELYSIN or MMP20, KLK4, DLX3, FAM83H, FAM20A WDR72…) coding for enamel matrix proteins, enamel matrix degrading proteins, proteins involved in hydroxyapatite formation and growth and mineralization processes have been discovered responsible for the clinical phenotypes (hypoplastic, hypomineralized, hypomature) encountered in AI.

Genes involved in enamel formation but not yet identified in association with any form of AI include: AMELY, AMELOBLASTIN, TUFTELIN, AMELOTIN, A Pin protein, ODAM (Odontogenic ameloblast associated).

In this research protocol the investigators explore the phenotype including the enamel ultrastructure and the genotype of a cohort of patients presenting AI.

Study Overview

• Status: Terminated
• Conditions: Amelogenesis Imperfecta
• Intervention / Treatment: Genetic: Salivary and blood sampling, as part of routine care. Collection of exfoliated teeth.

• Study Type: Observational
• Enrollment (Actual): 600

Contacts and Locations

Study Locations

• France
  • Alsace
    • Strasbourg, Alsace, France, 67091
      • Hopitaux Universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The recruitment of patients comes from several sources. A first cohort of 40 families is already followed by the reference center of Strasbourg. The reference center for rare diseases dental manifestations of Strasbourg recruiting patients at regional, interregional, national and international scale.

Description

Inclusion criteria:

• Patient presenting with AI
• New patient or patient already known in the center
• Child (in his primary dentition) or adult
• Man or woman
• Having signed a consent form or accepted to participate to the study
• Patient affiliated to social security
• Validation of the inclusion by the principal investigator looking at the patient file

Exclusion criteria:

• Patient with acquired enamel defects
• Patient whose clinical diagnostic is not possible
• Patient whose clinical file does not contain teeth photos
• Patient who has not signed a consent form and accepted to participate to the study
• Patient who is not affiliated to social security.
• Non validation of the inclusion by the principal investigator looking at the patient file

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Amelogenesis Imperfecta; Salivary and blood sampling, as part of routine care. Collection of exfoliated teeth	Genetic: Salivary and blood sampling, as part of routine care. Collection of exfoliated teeth.
healthy family members; Salivary and blood sampling, as part of routine care. Collection of exfoliated teeth	Genetic: Salivary and blood sampling, as part of routine care. Collection of exfoliated teeth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Natural history of Amelogenesis Imperfecta	Familial, medical, dental history	at day of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotype of Amelogenesis Imperfecta	Clinical and radiographic examination Type of enamel defects Associated dental or craniofacial anomalies	at day of enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic Bases of Amelogenesis Imperfecta	Genetic analysis	within 3 years after enrollment
Ultrastructure of teeth hard tissues	Ultrastructure analysis of teeth hard tissues	within 3 years after enrollment

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Principal Investigator: Bloch-Zupan Agnes, DChD, PhD, HDR, PU-PH, University Hospital of Strasbourg

Publications and helpful links

General Publications

• Prasad MK, Geoffroy V, Vicaire S, Jost B, Dumas M, Le Gras S, Switala M, Gasse B, Laugel-Haushalter V, Paschaki M, Leheup B, Droz D, Dalstein A, Loing A, Grollemund B, Muller-Bolla M, Lopez-Cazaux S, Minoux M, Jung S, Obry F, Vogt V, Davideau JL, Davit-Beal T, Kaiser AS, Moog U, Richard B, Morrier JJ, Duprez JP, Odent S, Bailleul-Forestier I, Rousset MM, Merametdijan L, Toutain A, Joseph C, Giuliano F, Dahlet JC, Courval A, El Alloussi M, Laouina S, Soskin S, Guffon N, Dieux A, Doray B, Feierabend S, Ginglinger E, Fournier B, de la Dure Molla M, Alembik Y, Tardieu C, Clauss F, Berdal A, Stoetzel C, Maniere MC, Dollfus H, Bloch-Zupan A. A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement. J Med Genet. 2016 Feb;53(2):98-110. doi: 10.1136/jmedgenet-2015-103302. Epub 2015 Oct 26.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2009
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: December 6, 2012
• First Posted (ESTIMATE): December 10, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 11, 2018
• Last Update Submitted That Met QC Criteria: July 10, 2018
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities; Stomatognathic Diseases; Tooth Diseases; Stomatognathic System Abnormalities; Tooth Abnormalities; Dental Enamel Hypoplasia; Amelogenesis Imperfecta
• Other Study ID Numbers: 4266