Am. J. Hum. Genet.

Thrombocytopenia–absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow’s milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR)

INTERACTIONS DES PROPRIÉTÉS PHOTOCONDUCTRICES ET ÉLECTRO-OPTIQUES DANS LES MATÉRIAUX FERRO-ÉLECTRIQUES ET APPLICATIONS

Dans cet article nous passons en revue les expériences effectuées lors de l'étude des variations d'indice de réfraction photo-induites dans les matériaux ferro-électriques. Nous exposons des résultats expérimentaux sur l'augmentation de la photosensibilité de ces matériaux par substitutions ioniques. Nous démontrons qu'il est possible d'engendrer, au voisinage des transitions de phases ferro-électriques, des structures en domaines susceptibles de conserver l'information enregistrée grâce aux champs de charges d'espaces photo-induits. Pour les matériaux de phases non polaires nous indiquons les perspectives d'applications à l'enregistrement optique et à la visualisation offertes par l'action des champs de charge d'espace photo-induits sur la caractéristique non linéaire de l'effet électro-optique.In this paper we review experiments related to the study of photo-induced variation of refractive index in ferro-electric materials. We expose experimental results about increase of photosensitivity by ionic substitutions. We give experimental evidence of generation, in the vicinity of phase transitions, of domain structures that keep the information previously recorded by means of photo-induced space charge field. For non polar materials we indicate possible applications to optical recording and visualization by using the action of photo-induced space charge fields on the non linear characteristic of electro-optic effect

Am. J. Hum. Genet.

Thrombocytopenia–absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow’s milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR)

Deletions of the RUNX2 gene are present in about 10% of individuals with cleidocranial dysplasia.

Contains fulltext : 88233.pdf (publisher's version ) (Closed access)Cleidocranial Dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by hypoplastic or absent clavicles, increased head circumference, large fontanels, dental anomalies, and short stature. Hand malformations are also common. Mutations in RUNX2 cause CCD, but are not identified in all CCD patients. In this study we screened 135 unrelated patients with the clinical diagnosis of CCD for RUNX2 mutations by sequencing analysis and demonstrated 82 mutations 48 of which were novel. By quantitative PCR we screened the remaining 53 unrelated patients for copy number variations in the RUNX2 gene. Heterozygous deletions of different size were identified in 13 patients, and a duplication of the exons 1 to 4 of the RUNX2 gene in one patient. Thus, heterozygous deletions or duplications affecting the RUNX2 gene may be present in about 10% of all patients with a clinical diagnosis of CCD which corresponds to 26% of individuals with normal results on sequencing analysis. We therefore suggest that screening for intragenic deletions and duplications by qPCR or MLPA should be considered for patients with CCD phenotype in whom DNA sequencing does not reveal a causative RUNX2 mutation.1 augustus 201

Quantal-like current fluctuations induced by odorants in olfactory receptor cells

Many sensory systems have evolved signal detection capabilities that are limited only by the physical attributes of the stimulus1. For example, \u2018hair\u2019 cells of the inner ear can detect displacements of atomic dimensions2. Likewise, both in vertebrates and in invertebrates photoreceptors can detect a single photon3, 4. The olfactory stimulus also has a quantal unit, the single odorant molecule. Insects are reportedly able to detect a single pheromone molecule5, whereas quantal responses in vertebrate olfactory receptor cells have not been reported yet. Psychophysical measurements indicate that a minimum of 50 odorant molecules are necessary for human olfactory detection, suggesting that an individual receptor may be activated by a single odorant molecule6. We report here measurements of current fluctuations induced by odorants that suggest a quantal event of about 0.3-1 pA, presumably triggered by the binding of a single odorant molecule. \ua9 1995, Nature Publishing Group. All rights reserved

Deletions of the RUNX2 Gene Are Present in About 10% of Individuals with Cleidocranial Dysplasia

Cleidocranial Dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by hypoplastic or absent clavicles, increased head circumference, large fontanels, dental anomalies, and short stature. Hand malformations are also common. Mutations in RUNX2 cause CCD, but are not identified in all CCD patients. In this study we screened 135 unrelated patients with the clinical diagnosis of CCD for RUNX2 mutations by sequencing analysis and demonstrated 82 mutations 48 of which were novel. By quantitative PCR we screened the remaining 53 unrelated patients for copy number variations in the RUNX2 gene. Heterozygous deletions of different size were identified in 13 patients, and a duplication of the exons 1 to 4 of the RUNX2 gene in one patient. Thus, heterozygous deletions or duplications affecting the RUNX2 gene may be present in about 10% of all patients with a clinical diagnosis of CCD which corresponds to 26% of individuals with normal results on sequencing analysis. We therefore suggest that screening for intragenic deletions and duplications by qPCR or MLPA should be considered for patients with CCD phenotype in whom DNA sequencing does not reveal a causative RUNX2 mutation. (C) 2010 Wiley-Liss, Inc

Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice

Odor stimulation of olfactory sensory neurons (OSNs) leads to both the activation and subsequent desensitization of a heteromultimeric cyclic-nucleotide-gated (CNG) channel present in these cells. The native olfactory CNG channel consists of three distinct subunits: CNGA2, CNGA4, and CNGB1b. Mice in which the CNGA4 gene has been deleted display defective Ca(2+)/calmodulin-dependent inhibition of the CNG channel, resulting in a striking reduction in adaptation of the odor-induced electrophysiological response in the OSNs. These mutants therefore afford an excellent opportunity to assess the importance of Ca(2+)-mediated CNG channel desensitization for odor discrimination and adaptation in behaving animals. By using an operant conditioning paradigm, we show that CNGA4-null mice are profoundly impaired in the detection and discrimination of olfactory stimuli in the presence of an adapting background odor. The extent of this impairment depends on both the concentration and the molecular identity of the adapting stimulus. Thus, Ca(2+)-dependent desensitization of the odor response in the OSNs mediated by the CNGA4 subunit is essential for normal odor sensation and adaptation of freely behaving mice, preventing saturation of the olfactory signal transduction machinery and extending the range of odor detection and discrimination