The Experts below are selected from a list of 981 Experts worldwide ranked by ideXlab platform
Tadashi Kajii - One of the best experts on this subject based on the ideXlab platform.
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Two Japanese cases with microcephalic primordial dwarfism: Classical Seckel Syndrome and osteodysplastic primordial dwarfism type II
Japanese journal of human genetics, 1993Co-Authors: Yoshitsugu Sugio, Masato Tsukahara, Tadashi KajiiAbstract:A male infant with “classical” Seckel Syndrome and a girl with osteodysplastic primordial dwarfism type II are described. The boy with classical Seckel Syndrome had severe brain dysplasia, a finding hitherto unreported in patients with this Syndrome. The patient with osteodysplastic dwarfism type II had skeletal abnormalities including lumbar scoliosis, a small and high pelvis, metaphyseal flaring of the distal radii and ulnae, V-shaped metaphyseal flaring of the distal femorae, and short metacarpals and phalanges. The mother of this girl was short, microcephalic, and had disproportionately short forearms and legs. In view of this, dominant inheritance of the disease was suggested.
Rena A Zinchenko - One of the best experts on this subject based on the ideXlab platform.
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Primary microcephaly case from the Karachay-Cherkess Republic poses an additional support for microcephaly and Seckel Syndrome spectrum disorders.
BMC medical genomics, 2018Co-Authors: Andrey V Marakhonov, Fedor A Konovalov, Amin Kh Makaov, Tatyana A Vasilyeva, Vitaly V Kadyshev, Varvara A Galkina, Elena L Dadali, Sergey I Kutsev, Rena A ZinchenkoAbstract:Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel Syndrome. Clinical exome sequencing of the proband revealed a novel homozygous single nucleotide deletion in ASPM gene, c.1386delC, resulting in preterm termination codon. Population screening reveals allele frequency to be less than 0.005. Mutations in this gene were not previously associated with Seckel Syndrome. Our case represents an additional support for the clinical continuum between Seckel Syndrome and primary microcephaly.
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primary microcephaly case from the karachay cherkess republic poses an additional support for microcephaly and Seckel Syndrome spectrum disorders
BMC Medical Genomics, 2018Co-Authors: Andrey V Marakhonov, Fedor A Konovalov, Amin Kh Makaov, Tatyana A Vasilyeva, Vitaly V Kadyshev, Varvara A Galkina, Elena L Dadali, Sergey I Kutsev, Rena A ZinchenkoAbstract:Background Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel Syndrome.
Sergey I Kutsev - One of the best experts on this subject based on the ideXlab platform.
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Primary microcephaly case from the Karachay-Cherkess Republic poses an additional support for microcephaly and Seckel Syndrome spectrum disorders.
BMC medical genomics, 2018Co-Authors: Andrey V Marakhonov, Fedor A Konovalov, Amin Kh Makaov, Tatyana A Vasilyeva, Vitaly V Kadyshev, Varvara A Galkina, Elena L Dadali, Sergey I Kutsev, Rena A ZinchenkoAbstract:Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel Syndrome. Clinical exome sequencing of the proband revealed a novel homozygous single nucleotide deletion in ASPM gene, c.1386delC, resulting in preterm termination codon. Population screening reveals allele frequency to be less than 0.005. Mutations in this gene were not previously associated with Seckel Syndrome. Our case represents an additional support for the clinical continuum between Seckel Syndrome and primary microcephaly.
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primary microcephaly case from the karachay cherkess republic poses an additional support for microcephaly and Seckel Syndrome spectrum disorders
BMC Medical Genomics, 2018Co-Authors: Andrey V Marakhonov, Fedor A Konovalov, Amin Kh Makaov, Tatyana A Vasilyeva, Vitaly V Kadyshev, Varvara A Galkina, Elena L Dadali, Sergey I Kutsev, Rena A ZinchenkoAbstract:Background Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel Syndrome.
Mark Odriscoll - One of the best experts on this subject based on the ideXlab platform.
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neuropathology of fetal stage Seckel Syndrome a case report providing a morphological correlate for the emerging molecular mechanisms
Brain & Development, 2012Co-Authors: Brendan Fitzgerald, Mark Odriscoll, Karen Chong, Sarah Keating, Patrick ShannonAbstract:Abstract Seckel Syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly and mental retardation. Pathological descriptions of fetal stage Seckel Syndrome are rare and pre-date the evolving understanding of the genetic and molecular mechanisms involved. The autopsy findings in a case of fetal Seckel Syndrome at 30 weeks gestation are presented, with detailed description of the neuropathological findings. Severe neurological abnormalities in a male fetus were observed that included microencephaly, cortical neuronal migration disorder, white matter tract hypoplasia/aplasia, premature depletion of the germinal matrix with cystic transformation and patchy absence of the external granular cell layer of the cerebellum. The striking neuropathological finding in this case was evidence of failure of the developing brain’s germinal elements, providing rare morphological insight into the abnormal development of the Seckel Syndrome fetal brain. The selective failure of this proliferating cell population correlates with the emerging molecular evidence that Seckel Syndrome is caused by defects in ATR-dependent DNA damage signaling with resultant premature death of proliferating cells.
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Seckel Syndrome exhibits cellular features demonstrating defects in the atr signalling pathway
Human Molecular Genetics, 2004Co-Authors: Gemma K Alderton, Penny A. Jeggo, Hans Joenje, Raymonda Varon, Anders D Borglum, Mark OdriscollAbstract:To 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.
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an overview of three new disorders associated with genetic instability lig4 Syndrome rs scid and atr Seckel Syndrome
DNA Repair, 2004Co-Authors: Mark Odriscoll, Andrew R Gennery, J Seidel, Patrick Concannon, Penny A. JeggoAbstract:Around 15–20 hereditary disorders associated with impaired DNA damage response mechanisms have been previously described. The range of clinical features associated with these disorders attests to the significant role that these pathways play during development. Recently, three new such disorders have been reported extending the importance of the damage response pathways to human health. LIG4 Syndrome is conferred by hypomorphic mutations in DNA ligase IV, an essential component of DNA non-homologous end-joining (NHEJ), and is associated with pancytopaenia, developmental and growth delay and dysmorphic facial features. Radiosensitive severe combined immunodeficiency (RS-SCID) is caused by mutations in Artemis, a protein that plays a subsidiary role in non-homologous end-joining although it is not an essential component. RS-SCID is characterised by severe combined immunodeficiency but patients have no overt developmental abnormalities. ATR-Seckel Syndrome is caused by mutations in ataxia telangiectasia and Rad3 related protein (ATR), a component of a DNA damage signalling pathway. ATR-Seckel Syndrome patients have dramatic microcephaly and marked growth and developmental delay. The clinical features of these patients are considered in the light of the function of the defective protein.
Yoshitsugu Sugio - One of the best experts on this subject based on the ideXlab platform.
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Two Japanese cases with microcephalic primordial dwarfism: Classical Seckel Syndrome and osteodysplastic primordial dwarfism type II
Japanese journal of human genetics, 1993Co-Authors: Yoshitsugu Sugio, Masato Tsukahara, Tadashi KajiiAbstract:A male infant with “classical” Seckel Syndrome and a girl with osteodysplastic primordial dwarfism type II are described. The boy with classical Seckel Syndrome had severe brain dysplasia, a finding hitherto unreported in patients with this Syndrome. The patient with osteodysplastic dwarfism type II had skeletal abnormalities including lumbar scoliosis, a small and high pelvis, metaphyseal flaring of the distal radii and ulnae, V-shaped metaphyseal flaring of the distal femorae, and short metacarpals and phalanges. The mother of this girl was short, microcephalic, and had disproportionately short forearms and legs. In view of this, dominant inheritance of the disease was suggested.
