1,301 research outputs found
Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling.
No full textContains fulltext :
70806.pdf (Publisher’s version ) (Closed access)Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size
Hechschar utwilas kelim enthaltend : Die Religions-Vorschriften bezüglich der Benützung von Geräthen zur Speise-Bereitung ...
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A CASE OF SECKEL SYNDROME WITH TRICUSPID ATRESIA
No full textA case of Seckel syndrome with tricuspid atresia: Seckel syndrome is an autosomal recessive disease presenting with marked growth retardation, microcephalic dwarfism, some facial and skeletal abnormalities. Tricuspid atresia is a rare and life threatening cyanotic congenital heart diseases, with an incidence of 1% to 3%. It is feature of the anatomically normally related great arteries with a large ventricular septum defect and stenosis of right ventricular outflow tract. Tricuspid atresia has never been reported in patients with Seckel syndrome. Here we report a 15-day-old girl baby diagnosed as having Seckel syndrome with tricuspid atresia
D. Seckel. Jenseits des Bildes, Anikonische Symbolik in der buddhistischen Kunst
No full textBareau André. D. Seckel. Jenseits des Bildes, Anikonische Symbolik in der buddhistischen Kunst. In: Revue de l'histoire des religions, tome 194, n°2, 1978. pp. 191-192
Seckel syndrome: A report of a case
No full textSeckel syndrome, first defined by Seckel in 1960, is a rare (incidence 1:10,000), genetically heterogeneous autosomal recessive disorder presenting at birth. This syndrome is characterized by a proportionate dwarfism of prenatal onset, a severe microcephaly with a "bird-headed" like appearance (beaked nose, receding forehead, prominent eyes, and micrognathia), and mental retardation. The significance of dental alterations in this syndrome resides in the defect, hypoplastic enamel, being limited to the primary dentition; in most instances the second primary molar tooth is not affected. A case of the Seckel syndrome is presented
Bird-Headed Dwarf of Seckel
No full textSeckel syndrome is an extremely rare inherited disorder characterized by growth delays prior to birth resulting in low birth weight. Growth delays continue after birth resulting in short stature (dwarfism). This syndrome is associated with an abnormally small head, varying degrees of mental retardation and unusual "beak like" protrusion of nose. Other facial features may include abnormally large eyes, a narrow face, malformed ears and an unusually small jaw. This syndrome has an autosomal recessive pattern of inheritance. A case of the Seckel syndrome is presented
Enfer [de la Bibliothèque nationale] : prohibition ou promotion de la littérature érotique ? (L\u27)
No full textIntervention de Raymond-Josué Seckel, responsable du Département de recherche bibliographique à la Bibliothèque nationale de France, lors de la journée thématique "Bibliothèques d\u27enfer(s) : interdits, contraintes et libertés en bibliothèque" organisée à l\u27enssib
Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway
No full textTo date, the only reported genetic defect identified in the developmental disorder, Seckel syndrome, is a mutation in ataxia telangiectasia and Rad3-related protein (ATR). Seckel syndrome is clinically and genetically heterogeneous and whether defects in ATR significantly contribute to Seckel syndrome is unclear. Firstly, we characterize ATR-Seckel cells for their response to DNA damage. ATR-Seckel cells display impaired phosphorylation of ATR-dependent substrates, impaired G2/M checkpoint arrest and elevated micronucleus (MN) formation following exposure to UV and agents that cause replication stalling. We describe a novel phenotype, designated nuclear fragmentation (NF), that occurs following replication arrest. Finally, we report that ATR-Seckel cells have an endogenously increased number of centrosomes in mitotic cells demonstrating a novel role for ATR in regulating centrosome stability. We exploit these phenotypes to examine cell lines derived from additional unrelated Seckel syndrome patients. We show that impaired phosphorylation of ATR-dependent substrates is a common but not invariant feature of Seckel syndrome cell lines. In contrast, all cell lines displayed defective G2/M arrest, increased levels of NF and MN formation following exposure to agents that cause replication stalling. All the Seckel syndrome cell lines examined showed increased endogenous centrosome numbers. Though ATR cDNA can complement the defects in ATR-Seckel cells, it failed to complement any of the additional cell lines. We conclude that Seckel syndrome represents a further damage response disorder that is uniquely associated with defects in the ATR-signalling pathway resulting in failed checkpoint arrest following exposure to replication fork stalling
Seckel syndrome in a family with three affected children and hematological manifestations associated with chromosome instability
No full textIn the present communication we report on a family with three children affected by Seckel-syndrome with mental deficiency, microcephaly, micrognathia and severe growth deficiency. All patients had chromosome instability, which was employed for the prenatal diagnosis of a fourth fetus suspected as a potential Seckel syndrome patient, and one of them had additional hematological disorders. As this condition has been previously characterized as a Seckel syndrome subgroup we report our data concerning this distinct entity.Genet Coun
Novel CENPJ mutation causes Seckel syndrome
No full textBackground Primordial dwarfism (PD) is an extremely rare, clinicallyheterogeneous condition characterised by profound prenatal and postnatal growth restriction among other manifestations that are helpful in the clinical classification. Recently, mutation of PCNT was reported in the context of two overlapping forms of PD: Seckel syndrome and Majewskiosteodysplastic primordial dwarfism type II (MOPDII). Aim To clinically and molecularly characterise a consanguineous family with Seckel syndrome. Methods Clinical evaluation, linkage analysis, homozygosity mapping and mutation analysis. Results Unexpectedly, linkage analysis led to the identification of a novel splice-site mutation in CENPJ that segregates with the phenotype in this family. Conclusion This report establishes for the first time that mutation of CENPJ can lead to Seckel syndrome and calls for further investigation of the role played by other microcephaly related genes in the pathogenesis of PD
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