38 research outputs found
Hemangiome caverneux mandibulaire - A propos d'un cas
L'hémangiome caverneux est une rare tumeur osseuse qui se caractérise par la prolifération de vaisseaux sanguins dilatés bordés de cellules endothéliales.La localisation préférentielle est crâniennene et vertébrale. Au niveau du massif facial, la localisation au niveau des maxillaires est la plus fréquente. La symptomatologie est souvent discrète et le diagnostic est tardif au stade de l'assymétrie faciale. L'imagerie objective une masse tissulaire se rehaussant fortement après injection de produit de contraste. plusieurs traitements ont été proposés mais le traitement de choix reste la chirurgieavec embolisation. Nous raportons le cas original d'une localisation mandibulaire chez une jeune patiente de 28 ans et nous nous proposons de discuter les différents aspects cliniques, paracliniques et thérapeutiques de cette pathologie.MOTS CLES: Hémangiome; Caverneux; Mandibule
De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development
Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD
Homozygous frameshift mutations in FAT1 cause a syndrome characterized by colobomatous-microphthalmia, ptosis, nephropathy and syndactyly
A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic fissure fusion during vertebrate eye development. Our findings establish FAT1 as a gene with pleiotropic effects in human, in that frameshift mutations cause a severe multi-system disorder whereas recessive missense mutations had been previously associated with isolated glomerulotubular nephropathy
De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development
Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD
SMCHD1 is involved in de novo methylation of the DUX4-encoding D4Z4 macrosatellite
The DNA methylation epigenetic signature is a key determinant during development. Rules governing its establishment and maintenance remain elusive especially at repetitive sequences, which account for the majority of methylated CGs. DNA methylation is altered in a number of diseases including those linked to mutations in factors that modify chromatin. Among them, SMCHD1 (Structural Maintenance of Chromosomes Hinge Domain Containing 1) has been of major interest following identification of germline mutations in Facio-Scapulo-Humeral Dystrophy (FSHD) and in an unrelated developmental disorder, Bosma Arhinia Microphthalmia Syndrome (BAMS). By investigating why germline SMCHD1 mutations lead to these two different diseases, we uncovered a role for this factor in de novo methylation at the pluripotent stage. SMCHD1 is required for the dynamic methylation of the D4Z4 macrosatellite upon reprogramming but seems dispensable for methylation maintenance. We find that FSHD and BAMS patient's cells carrying SMCHD1 mutations are both permissive for DUX4 expression, a transcription factor whose regulation has been proposed as the main trigger for FSHD. These findings open new questions as to what is the true aetiology for FSHD, the epigenetic events associated with the disease thus calling the current model into question and opening new perspectives for understanding repetitive DNA sequences regulation
Enhancing Supply Chain Agility by Deploying Competence Management and the Supply Chain Operations Model
Currently, business environment is characterized by pressure caused by stiff competition, constant changes (e.g., product/ technological innovations, decreasing product lifecycles, and product proliferation), and a high level of market uncertainty band unpredictability. The agility of the Supply Chain Management (SCM) is clearly identified as a key factor for success and a strategic essential lever. This paper explores the impact of deploying competence management and Supply Chain Operations Reference (SCOR) model on firm performance. Our approach is based on a systemic view by considering the SCOR reference model as the heart of competence management system
Clinical and molecular report of c.1331 + 1G > A mutation of the AAAS gene in a Moroccan family with Allgrove syndrome: a case report
Abstract Background Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of achalasia, alacrimia and adrenal insufficiency. It is caused by the mutations of the AAAS gene located on chromosome 12q13. The c.1331 + 1G > A mutation is one of the most common described in North Africa including Tunisia, Algeria and Libya. We report here the clinical and genetic profile of a Moroccan family with Allgrove syndrome. Case presentation A Moroccan sister and brother born to consanguineous parents were found, at the ages of twelve and fifteen months old respectively, to have alacrimia and isolated glucocorticoid deficiency. Later, they developed achalasia whereupon Allgrove syndrome was diagnosed clinically and confirmed by DNA sequencing which revealed a c.1331 + 1G > A mutation in the AAAS gene. Conclusion This finding reinforces previous studies in demonstrating the geographic expansion of the ancestral mutation c.1331 + 1G > A in North African patients and thus enabling targeted genetic counseling. To the best of our knowledge, this is the first report of the AAAS gene mutation in Moroccan patients
Report of the First Clinical Case of a Moroccan Kabuki Patient with a Novel MLL2 Mutation
Kabuki syndrome (also known as Niikawa-Kuroki syndrome)
is a rare autosomal disorder, characterized by an unusual
face, short stature, skeletal, visceral and dermatoglyphic abnormalities,
cardiac anomalies, mental retardation, and immunological
defects. Point mutations and large intragenic
deletions and duplications of the mixed lineage leukemia
2 (MLL2) and exons deletions of lysine demethylase 6A
( KDM6A) genes have been identified as its underlying causes.
We report on the first description of a Moroccan Kabuki syndrome
patient with typical facial features, developmental
delay, finger pads, and other anomalies carrying a novel
splice site mutation in the MLL2 gene that produces a truncated
and likely pathogenetic form of MLL2 protein