An atypical 7q11.23 deletion in a normal IQ Williams-Beuren syndrome patient.

Williams-Beuren syndrome (WBS; OMIM no. 194050) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion of 1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features. These insights for genotype-phenotype correlations came from the molecular and clinical analysis of patients with atypical deletions and mice models. Here we report a patient showing mild WBS physical phenotype and normal IQ, who carries a shorter 1 Mb atypical deletion. This rearrangement does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the hypothesis that hemizygosity of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms and in the specific motor and cognitive deficits observed in WBS patients.

The Vth "prapāṭhaka" of the Vādhūlaśrautasūtra

Résumé/Summary : La thèse présentée ici et intitulée The Vth prapāṭhaka of the Vādhūlaśrautasūtra consiste en une édition critique suivie d'une traduction et d'un commentaire du Ve chapitre (prapāṭhaka) du Vādhūlaśrautasūtra consacré au sacrifice animal dit "indépendant" (nirūḍhapaśubandha) de la religion védique. La traduction et le commentaire font l'objet du premier tome de cette thèse et l'édition critique celui du second tome. Le commentaire qui suit la traduction dans le premier tome ne se limite pas aux particularités de la version Vādhūla du nirūḍhapaśubandha. Il s'agit plutôt d'une série de monographies consacrées à des aspects particuliers du sacrifice animal décrit par les Veda, voire à des questions plus générales d'exégèse des textes védiques. Dans ma conclusion à la fin du premier tome je discute aussi de l'antiquité de l'école Vādhūla et de sa place dans le corpus textuel de la branche Taittirīya du Yajurveda noir. THE PRESENT THESIS, ENTITLED THE VTH PRAPAṭHAKA OF THE VADHULASRAUTASUTRA, CONSISTS IN A CRITICAL EDITION, FOLLOWED BY A TRANSLATION AND A COMMENTARY, OF THE VTH CHAPTER (PRAPAṭHAKA) OF THE VADHULASRAUTASUTRA. THE VTH PRAPAṭHAKA IS DEDICATED TO THE DESCRIPTION OF THE SO-CALLED "INDEPENDENT" ANIMAL SACRIFICE (NIRUḍHAPASUBANDHA) IN VEDIC RELIGION. THE TRANSLATION AND THE COMMENTARY ARE PRESENTED IN THE FIRST VOLUME, WHILE THE CRITICAL EDITION MAKES UP THE SECOND VOLUME. The commentary that follows the translation in the first volume is not concerned only with the peculiarities of the Vādhūla version of the nirūḍhapaśubandha. It is more a series of short monographs related to particular aspects of the animal sacrifice described in the Veda and to problems of exegesis of Vedic texts. In my conclusion at the end of the first volume, I also discuss the ancientness of the Vādhūla school, as well as its place within the corpus of Taittirīya texts.

FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone.

The functional interaction between fibroblast growth factor 23 (FGF-23) and Klotho in the control of vitamin D and phosphate homeostasis is manifested by the largely overlapping phenotypes of Fgf23- and Klotho-deficient mouse models. However, to date, targeted inactivation of FGF receptors (FGFRs) has not provided clear evidence for an analogous function of FGFRs in this process. Here, by means of pharmacologic inhibition of FGFRs, we demonstrate their involvement in renal FGF-23/Klotho signaling and elicit their role in the control of phosphate and vitamin D homeostasis. Specifically, FGFR loss of function counteracts renal FGF-23/Klotho signaling, leading to deregulation of Cyp27b1 and Cyp24a1 and the induction of hypervitaminosis D and hyperphosphatemia. In turn, this initiates a feedback response leading to high serum levels of FGF-23. Further, we show that FGFR inhibition blocks Fgf23 transcription in bone and that this is dominant over vitamin D-induced Fgf23 expression, ultimately impinging on systemic FGF-23 protein levels. Additionally, we identify Fgf23 as a specific target gene of FGF signaling in vitro. Thus, in line with Fgf23- and Klotho-deficient mouse models, our study illustrates the essential function of FGFRs in the regulation of vitamin D and phosphate levels. Further, we reveal FGFR signaling as a novel in vivo control mechanism for Fgf23 expression in bone, suggesting a dual function of FGFRs in the FGF-23/Klotho pathway leading to vitamin D and phosphate homeostasis.