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Baujat G.,University of Paris Descartes | Laplanche J.-L.,Unite Fonctionnelle de Genetique Moleculaire | Daire V.C.,University of Paris Descartes | Collet C.,Unite Fonctionnelle de Genetique Moleculaire
European Journal of Human Genetics | Year: 2014

TCF12 mutations have been reported very recently in coronal synostosis. We report several cases of familial coronal synostosis among four families harbouring novel TCF12 mutations. We observed a broad interfamilial phenotypic spectrum with features overlapping with the Saethre-Chotzen syndrome. TCF12 molecular testing should be considered in patients with unilateral- or bilateral-coronal synostosis associated or not with syndactyly, after having excluded mutations in the TWIST1 gene and the p.Pro250Arg mutation in FGFR3.European Journal of Human Genetics advance online publication, 16 April 2014; doi:10.1038/ejhg.2014.57.

Dupont C.,Unite Fonctionnelle de Cytogenetique | Bucourt M.,Laboratoire Of Foetopathologie | Guimiot F.,Service de Biologie du Developpement | Guimiot F.,University Paris Diderot | And 12 more authors.
Molecular Cytogenetics | Year: 2014

Background: Roberts syndrome (RBS) is a rare autosomal recessive disorder mainly characterized by growth retardation, limb defects and craniofacial anomalies. Characteristic cytogenetic findings are "railroad track" appearance of chromatids and premature centromere separation in metaphase spreads. Mutations in the ESCO2 (establishment of cohesion 1 homolog 2) gene located in 8p21.1 have been found in several families. ESCO2, a member of the cohesion establishing complex, has a role in the effective cohesion between sister chromatids. In order to analyze sister chromatids topography during interphase, we performed 3D-FISH using pericentromeric heterochromatin probes of chromosomes 1, 4, 9 and 16, on preserved nuclei from a fetus with RBS carrying compound heterozygous null mutations in the ESCO2 gene.Results: Along with the first observation of an abnormal separation between sister chromatids in heterochromatic regions, we observed a statistically significant change in the intranuclear localization of pericentromeric heterochromatin of chromosome 1 in cells of the fetus compared to normal cells, demonstrating for the first time a modification in the spatial arrangement of chromosome domains during interphase.Conclusion: We hypothesize that the disorganization of nuclear architecture may result in multiple gene deregulations, either through disruption of DNA cis interaction -such as modification of chromatin loop formation and gene insulation - mediated by cohesin complex, or by relocation of chromosome territories. These changes may modify interactions between the chromatin and the proteins associated with the inner nuclear membrane or the pore complexes. This model offers a link between the molecular defect in cohesion and the complex phenotypic anomalies observed in RBS. © 2014 Dupont et al.; licensee BioMed Central Ltd.

Legendre M.,Unite Fonctionnelle de Genetique Moleculaire | Legendre M.,University Pierre and Marie Curie | Cohen E.,University Pierre and Marie Curie | Amselem S.,Unite Fonctionnelle de Genetique Moleculaire | Amselem S.,University Pierre and Marie Curie
Correspondances en MHND | Year: 2015

To date, only about ten genes are known to be responsible for adrenocorticotropic hormone (ACTH) deficits, either isolated or integrated into combined pituitary hormone deficits. TBX19 defects are the main cause for isolated ACTH deficit. Biallelic mutations in this gene are responsible for half of the deficits in neonates. Detailed clinical and biological data, together with family history, are required to address the most likely transmission mode and the genes that are to be analyzed. Based on genetic test results, genetic counseling can be offered to the patient and her/his relatives. For dominant syndromic forms associated with variable expression and incomplete penetrance, genetic counseling can be difficult (GLI2 for instance). Knowing the exact etiology of the deficit in the proband allows appropriate neonatal care for her/his relatives. It is also a prerequisite for a potential prenatal diagnosis for the most severe syndromic forms.

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