A Novel Mutation Involving the Initiation Codon of FGF3 in a Family Described with Complete Inner Ear Agenesis, Microtia and Major Microdontia (LAMM Syndrome)

LAMM syndrome (OMIM #610706) is a rare autosomal recessive syndrome characterized by the association of Michel aplasia, microdontia and malformation of the external ear. Different mutations in FGF3 gene were reported in several families presenting with this syndrome. Clinical features and genetic results observed in a family with LAMM syndrome are reported. The diagnosis of isolated Michel aplasia was initially made in this family composed of two affected children. Microtia and microdontia was recently evidenced in both patients suggesting the diagnosis of LAMM syndrome. New auditory and orodental iconography was performed permitting to describe the patients’ phenotype in depth and to report rare findings of LAMM syndrome. The sequencing of FGF3 gene identified a novel missense mutation (c.2T>G), substituting the first initiator methionine in arginine, in the fibroblast growth factor 3 (FGF3) at the homozygous state in both patients. LAMM syndrome was confirmed and appropriate genetic counseling performed

An Inhibitory Sex Pheromone Tastes Bitter for Drosophila Males

Sexual behavior requires animals to distinguish between the sexes and to respond appropriately to each of them. In Drosophila melanogaster, as in many insects, cuticular hydrocarbons are thought to be involved in sex recognition and in mating behavior, but there is no direct neuronal evidence of their pheromonal effect. Using behavioral and electrophysiological measures of responses to natural and synthetic compounds, we show that Z-7-tricosene, a Drosophila male cuticular hydrocarbon, acts as a sex pheromone and inhibits male-male courtship. These data provide the first direct demonstration that an insect cuticular hydrocarbon is detected as a sex pheromone. Intriguingly, we show that a particular type of gustatory neurons of the labial palps respond both to Z-7-tricosene and to bitter stimuli. Cross-adaptation between Z-7-tricosene and bitter stimuli further indicates that these two very different substances are processed by the same neural pathways. Furthermore, the two substances induced similar behavioral responses both in courtship and feeding tests. We conclude that the inhibitory pheromone tastes bitter to the fly

Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder

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

Leucémie lymphoblastique aiguë avec irradiation massive : échec orthodontique programmé ?

Objectif Les irradiations massives utilisées dans le traitement de certains cancers agissent, sans discernement, sur la multiplication cellulaire. Au niveau de la sphère oro-faciale, chez l'enfant en croissance lorsque la dentition n'est pas achevée, ce type de traitement affecte particulièrement le développement et l'éruption des dents encore immatures : hypoplasies et dents incluses sont le lot commun des jeunes individus ayant été exposés aux irradiations. Matériel, résultat et discussion Le patient décrit a été vu la première fois en consultation orthodontique à l'âge de douze ans, après un traitement par irradiation corporelle à l'âge de huit ans. Diverses complications liées à la greffe n'ont pas permis d'intervention orthodontique jusqu'à l'âge de quinze ans. Les clichés radiologiques réguliers effectués pendant cette période ont mis en évidence l'arrêt de l'évolution et l'inclusion des 13, 33, 43, 17, 27, 37, 47. La dose d'irradiation chez ce patient avait été de 12 Gray, dose inférieure au seuil critique de risque pour l'ostéoradionécrose (40 Gray). Malgré le pronostic défavorable de voir évoluer ces dents, une tentative de mise en place orthodontico-chirurgicale a été programmée sur la 33. En réponse à cette sollicitation orthodontique la dent s'est mobilisée et a pu être déplacée et guidée en bonne place sur l'arcade, contre toute attente. Conclusion Le guidage orthodontique de dents restées incluses après irradiation massive est une option thérapeutique qui peut être envisagée avec succès

All-Materials-Inclusive Flash Spark Plasma Sintering

Abstract A new flash (ultra-rapid) spark plasma sintering method applicable to various materials systems, regardless of their electrical resistivity, is developed. A number of powders ranging from metals to electrically insulative ceramics have been successfully densified resulting in homogeneous microstructures within sintering times of 8–35 s. A finite element simulation reveals that the developed method, providing an extraordinary fast and homogeneous heating concentrated in the sample’s volume and punches, is applicable to all the different samples tested. The utilized uniquely controllable flash phenomenon is enabled by the combination of the electric current concentration around the sample and the confinement of the heat generated in this area by the lateral thermal contact resistance. The presented new method allows: extending flash sintering to nearly all materials, controlling sample shape by an added graphite die, and an energy efficient mass production of small and intermediate size objects. This approach represents also a potential venue for future investigations of flash sintering of complex shapes

Dental and extra-oral clinical features in 41 patients with WNT10A gene mutations: a multicentric genotype-phenotype study.

WNT10A gene encodes a canonical wingless pathway signaling molecule involved in cell fate specification as well as morphogenetic patterning of the developing ectoderm, nervous system, skeleton, and tooth. In patients, WNT10A mutations are responsible for ectodermal-derived pathologies including isolated hypo-oligodontia, tricho-odonto-onycho-dermal dysplasia (TOODD) and Schöpf-Schulz-Passarge Syndrome (SSPS). Here we describe the dental, ectodermal, and extra-ectodermal phenotypic features of a cohort of 41 patients from 32 unrelated families. Correlations with WNT10A molecular status (heterozygous carrier, compound heterozygous, homozygous) and patient's phenotypes were performed. Mild to severe oligodontia was observed in all patients bearing biallelic WNT10A mutations. However, patients with compound heterozygous mutations presented no significant difference in phenotypes compared to homozygous individuals. Anomalies in tooth morphology were frequently observed with heterozygous patients displaying hypodontia. No signs of SSPS, especially eyelids cysts, were detected in our cohort. Interestingly, extra-ectodermal signs consisted of skeletal, neurological and vascular anomalies, the latter suggesting a wider phenotypic spectrum associated with WNT10A mutations. Indeed, the Wnt pathway plays a crucial role in skeletal development, lipid metabolism, and neurogenesis, potentially explaining patient's clinical manifestations.journal article2017 Jan 202017 01 20importe