Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetic and prenatal findings in two Japanese patients with Schinzel-Giedion syndrome.

ABSTRACT: We report two Japanese patients with Schinzel-Giedion syndrome. When polyhydramnios is observed, additional fetal findings such as overlapping fingers, hydrocephalus, hydronephrosis, and very characteristic facial appearance comprising high, prominent forehead, hypertelorism, and depressed nasal root may suggest Schinzel-Giedion syndrome.

SUBMITTER: Hishimura N

PROVIDER: S-EPMC5224771 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genetic and prenatal findings in two Japanese patients with Schinzel-Giedion syndrome.

Hishimura Nozomi N Watari Michiko M Ohata Hiroki H Fuseya Naho N Wakiguchi Sadae S Tokutomi Tomoharu T Okuhara Kouji K Takahashi Nobuhiro N Iizuka Susumu S Yamamoto Hiroshi H Mishima Takashi T Fujieda Satoko S Kobayashi Ryoji R Cho Kazutoshi K Kuroda Yukiko Y Kurosawa Kenji K Tonoki Hidefumi H

Clinical case reports 20161117 1

We report two Japanese patients with Schinzel-Giedion syndrome. When polyhydramnios is observed, additional fetal findings such as overlapping fingers, hydrocephalus, hydronephrosis, and very characteristic facial appearance comprising high, prominent forehead, hypertelorism, and depressed nasal root may suggest Schinzel-Giedion syndrome. ...[more]

PMID: 28096980

Similar Datasets

Scoliosis in a case of Schinzel-Giedion syndrome.

Project description:Schinzel-Giedion syndrome (SGS) is a rare disorder characterized by midface retraction, hypertrichosis, and multiple skeletal anomalies with severe mental retardation. Various skeletal manifestations of the disease have been previously described. We present the first case of SGS developing scoliosis. The patient presented with scoliosis at the age of 8 years which rapidly progressed to severe thoraco-lumbar scoliosis. Survival beyond 2 years is rare in this syndrome. The objective of this report is to describe the possibility of development of scoliosis in SGS due to the neuromuscular nature of the syndrome, especially in long survivors.

| S-EPMC2744749 | biostudies-other

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies.

Project description:Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype.

| S-EPMC5386295 | biostudies-literature

Molecular signature of Schinzel-Giedion syndrome in human neural progenitors

Project description:Schinzel-Giedion syndrome (SGS) is a developmental syndrome, due to the accumulation of SETBP1 protein, which is fatal in early infancy. SGS has a multi-organ involvement with severe and persistent intellectual and physical problems. We produced a human SGS model that outlines disease-relevant phenotypes using patient-derived induced pluripotent stem cells and isogenic controls. Whole transcriptome profiling describes cancer-like alterations in SGS neural progenitors including deregulation of oncogenes and suppressors and enhanced proliferation. These findings demonstrated how SGS post-natal pathological traits mayhave developmental origin in the failure of controlling cell identity and homeostasis due to SETBP1 protein accumulation.

2021-06-03 | GSE150810 | GEO

SETBP1 accumulation induces P53 inhibition and genotoxic stress in neural progenitors underlying neurodegeneration in Schinzel-Giedion syndrome.

Project description:The investigation of genetic forms of juvenile neurodegeneration could shed light on the causative mechanisms of neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome caused by mutations in the SETBP1 gene, inducing the accumulation of its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here we introduce a human SGS model that displays disease-relevant phenotypes. We show that SGS neural progenitors exhibit aberrant proliferation, deregulation of oncogenes and suppressors, unresolved DNA damage, and resistance to apoptosis. Mechanistically, we demonstrate that high SETBP1 levels inhibit P53 function through the stabilization of SET, which in turn hinders P53 acetylation. We find that the inheritance of unresolved DNA damage in SGS neurons triggers the neurodegenerative process that can be alleviated either by PARP-1 inhibition or by NAD + supplementation. These results implicate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis.

| S-EPMC8245514 | biostudies-literature

Cell-type-specific gene expression and regulation in the cerebral cortex and kidney of atypical Setbp1<sup>S858R</sup> Schinzel Giedion Syndrome mice.

Project description:Schinzel Giedion Syndrome (SGS) is an ultra-rare autosomal dominant Mendelian disease presenting with abnormalities spanning multiple organ systems. The most notable phenotypes involve severe developmental delay, progressive brain atrophy, and drug-resistant seizures. SGS is caused by spontaneous variants in SETBP1, which encodes for the epigenetic hub SETBP1 transcription factor (TF). SETBP1 variants causing classical SGS cluster at the degron, disrupting SETBP1 protein degradation and resulting in toxic accumulation, while those located outside cause milder atypical SGS. Due to the multisystem phenotype, we evaluated gene expression and regulatory programs altered in atypical SGS by snRNA-seq of the cerebral cortex and kidney of Setbp1S858R heterozygous mice (corresponds to the human likely pathogenic SETBP1S867R variant) compared to matched wild-type mice by constructing cell-type-specific regulatory networks. Setbp1 was differentially expressed in excitatory neurons, but known SETBP1 targets were differentially expressed and regulated in many cell types. Our findings suggest molecular drivers underlying neurodevelopmental phenotypes in classical SGS also drive atypical SGS, persist after birth, and are present in the kidney. Our results indicate SETBP1's role as an epigenetic hub leads to cell-type-specific differences in TF activity, gene targeting, and regulatory rewiring. This research provides a framework for investigating cell-type-specific variant impact on gene expression and regulation.

| S-EPMC10660642 | biostudies-literature

Single cell profiling of the cerebral organoids derived from Schinzel-Giedion syndrome cells and isogenic controls

Project description:Schinzel-Giedion syndrome (SGS) is a developmental syndrome, due to SETBP1 gene mutations inducing the accumulation of the relative protein, which is fatal in early infancy. Here, we generated unpatterned cerebral organoids from both SGS iPSC line and isogenic control line (through CRISPR/Cas9 back correction). We showed that SEBP1 accumulation triggers the development of large and convoluted epithelial folds in SGS cerebral organoids. To thoroughly characterize the 3D organoids we used scRNAseq (10X platform) in which we evidences the presence of both neural progenitors and committed neural progenitors with aberrant gene signature in SGS organoids that possibly sustain the lateral increase of the neuroepithelium

2021-06-03 | GSE171263 | GEO

Cell-type-specific expression and regulation in cerebral cortex and kidney of atypical Schinzel Giedion Syndrome mice

Project description:Schinzel Giedion Syndrome (SGS) is an ultra rare progressive neurodegenerative disease affecting less than 100 inividuals worldwide. SGS is cuased by variants in SETBP1 gene. We used snRNA-seq of cerebral cortex and kidney tissues from mice carrying a heterozygous S858R variant in Setbp1 and constructed cell-type-specific gene regulatory networks to profile the impact of the point mutation on cell-type-specific expression and regulation of Setbp1 and its known targets in atypical SGS. Grant Number: 1U54oD030167 UAB Pilot Center for Precision Animal Modeling (C-PAM) Grantee: Brittany Lasseigne Grant Number: 5T32GM008111-35 UAB CMDB T32 Grantee: Jordan Whitlock

2023-10-16 | GSE237816 | GEO

SETBP1 accumulation induces P53 inhibition and genotoxic stress in neural progenitors underlying neurodegeneration in Schinzel-Giedion syndrome

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-03 | GSE171266 | GEO