Orodental phenotype and genotype findings in all subtypes of hypophosphatasia

<p>Abstract</p> <p>Background</p> <p>Hypophosphatasia (HP) is a rare inherited disorder characterized by a wide spectrum of defects in mineralized tissues and caused by deficiency in the tissue non-specific alkaline phosphatase gene (<it>ALPL</it>). The symptoms are highly variable in their clinical expression, and relate to numerous mutations in this gene. The first clinical sign of the disease is often a premature loss of deciduous teeth, mostly in the moderate forms.</p> <p>Aim</p> <p>The purpose of this study was to document the oral features of HP patients and to relate theses features to the six recognized forms of HP in 5 patients with known genotype and to investigate the genotype-phenotype correlations.</p> <p>Methods</p> <p>Clinical and radiographic examinations were carried out. We collected medical and dental history in the kindred and biochemical data. Finally, mutations in the <it>ALPL </it>gene were tested by DNA sequencing in SESEP laboratory.</p> <p>Results</p> <p>We have for the first time related the known dental anomalies which occur as integral features of HP to the recognized clinical forms of HP. We also pointed out striking dental abnormalities which were never described in association with this rare disease. Accurate genotype-phenotype severity correlations were observed.</p> <p>Conclusion</p> <p>This work allowed us to compare orodental manifestations in all the clinical forms of HP within the patient's sample. According to the severity of the disorder, some dental defects were infrequent, while other were always present. The long term prognosis of the permanent teeth varies from a patient to another. As premature loss of primary teeth is often the first, and sometimes the only visible symptom of the milder forms, the paediatric dentist plays a critical role in the detection and diagnosis of the disease.</p

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

Caracterisation immunohistochimique des cellules inflammatoires et des cellules parenchymateuses en pathologie renale

SIGLEINIST T 77520 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Prévention et accès aux soins bucco-dentaires des enfants porteurs de handicaps (enquête dans cinq institutions de la région Lorraine)

L'heure est aujourd'hui à la compensation du handicap, comme la loi 2005 pour l'égalité des chances le stipule. Dans les cinq établissements que nous avons visités, la prise en charge de l'hygiène bucco-dentaire est effectuée par le personnel éducatif, ces personnes n'ont reçu aucune formation à ce sujet. Les personnes interrogées trouvent majoritairement que le brossage et les soins de bouche sont longs et difficiles, mais ils sont 96% à les considérer obligatoires. La situation de la prévention et de l'accès aux soins destinés aux enfants porteurs de handicap est préoccupante. Pourtant de nombreux moyens ont été définis pour les améliorer. Les acteurs en santé publique sont unanimes : pour eux, la mise en place de réseaux est la meilleure voie pour qu'en France les personnes en situation de handicaps ne restent pas en marge du système de soins bucco-dentaires.NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocSudocFranceF

Etude rétrospective anatomo-clinique de 59 observations d'amylose rénale AA recueillies entre janvier 1990 et décembre 2000 dans trois centres parisiens de pathologie rénale

Centre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Système A.R.T. (Atraumatic Restorative Treatment) (un nouveau système thérapeutique de restauration atraumatique pour la carie dentaire)

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prise en charge non pharmacologique de l enfant en refus de soins en odontologie

NANCY1-Bib. numérique (543959902) / SudocSudocFranceF