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Neurology India 2022
Topics: Humans; Sneddon Syndrome; Skin
PubMed: 36537441
DOI: 10.4103/0028-3886.364083 -
Neurology India 2023
Topics: Humans; Sneddon Syndrome; Skin
PubMed: 37635563
DOI: 10.4103/0028-3886.383840 -
The Pan African Medical Journal 2019
PubMed: 31762878
DOI: 10.11604/pamj.2019.34.9.11903 -
The Israel Medical Association Journal... Oct 2020
Topics: Fatigue; Female; Humans; Leg; Magnetic Resonance Imaging; Middle Aged; Sneddon Syndrome
PubMed: 33070495
DOI: No ID Found -
Nature Communications Nov 2018Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in...
Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation in CHD3, identified during whole genome sequencing of a cohort of children with rare speech disorders. To gain a comprehensive view of features associated with disruption of this gene, we use a genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3 mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase domain of the encoded protein. Modeling their impact on the three-dimensional structure demonstrates disturbance of critical binding and interaction motifs. Experimental assays with six of the identified mutations show that a subset directly affects ATPase activity, and all but one yield alterations in chromatin remodeling. We implicate de novo CHD3 mutations in a syndrome characterized by intellectual disability, macrocephaly, and impaired speech and language.
Topics: Adenosine Triphosphatases; Child, Preschool; Chromatin Assembly and Disassembly; DNA Helicases; Developmental Disabilities; Female; Gene Expression; Genotype; HEK293 Cells; Humans; Intellectual Disability; Language Disorders; Male; Megalencephaly; Mi-2 Nucleosome Remodeling and Deacetylase Complex; Models, Molecular; Mutation, Missense; Neurodevelopmental Disorders; Phenotype; Protein Domains; Speech Disorders; Whole Genome Sequencing
PubMed: 30397230
DOI: 10.1038/s41467-018-06014-6 -
American Journal of Human Genetics Jan 2018Histone lysine methyltransferases (KMTs) and demethylases (KDMs) underpin gene regulation. Here we demonstrate that variants causing haploinsufficiency of KMTs and KDMs...
Histone lysine methyltransferases (KMTs) and demethylases (KDMs) underpin gene regulation. Here we demonstrate that variants causing haploinsufficiency of KMTs and KDMs are frequently encountered in individuals with developmental disorders. Using a combination of human variation databases and existing animal models, we determine 22 KMTs and KDMs as additional candidates for dominantly inherited developmental disorders. We show that KMTs and KDMs that are associated with, or are candidates for, dominant developmental disorders tend to have a higher level of transcription, longer canonical transcripts, more interactors, and a higher number and more types of post-translational modifications than other KMT and KDMs. We provide evidence to firmly associate KMT2C, ASH1L, and KMT5B haploinsufficiency with dominant developmental disorders. Whereas KMT2C or ASH1L haploinsufficiency results in a predominantly neurodevelopmental phenotype with occasional physical anomalies, KMT5B mutations cause an overgrowth syndrome with intellectual disability. We further expand the phenotypic spectrum of KMT2B-related disorders and show that some individuals can have severe developmental delay without dystonia at least until mid-childhood. Additionally, we describe a recessive histone lysine-methylation defect caused by homozygous or compound heterozygous KDM5B variants and resulting in a recognizable syndrome with developmental delay, facial dysmorphism, and camptodactyly. Collectively, these results emphasize the significance of histone lysine methylation in normal human development and the importance of this process in human developmental disorders. Our results demonstrate that systematic clinically oriented pathway-based analysis of genomic data can accelerate the discovery of rare genetic disorders.
Topics: Adolescent; Child; Child, Preschool; Developmental Disabilities; Female; Haploinsufficiency; Histone Demethylases; Histone-Lysine N-Methyltransferase; Humans; Male; Mutation
PubMed: 29276005
DOI: 10.1016/j.ajhg.2017.11.013 -
JAAD Case Reports May 2021
PubMed: 33912636
DOI: 10.1016/j.jdcr.2021.03.023 -
Proceedings of the Royal Society of... Nov 1977
Topics: Female; Humans; Male; Malingering; Munchausen Syndrome; Self Mutilation; Skin Diseases
PubMed: 601049
DOI: No ID Found -
Nefrologia 2021
PubMed: 32234261
DOI: 10.1016/j.nefro.2020.01.001 -
Orphanet Journal of Rare Diseases Dec 2014Sneddon's syndrome (SS) is a rare non-inflammatory thrombotic vasculopathy characterized by the combination of cerebrovascular disease with livedo racemosa(LR). The... (Review)
Review
Sneddon's syndrome (SS) is a rare non-inflammatory thrombotic vasculopathy characterized by the combination of cerebrovascular disease with livedo racemosa(LR). The Orpha number for SS is ORPHA820. It has been estimated that the incidence of SS is 4 per 1 million per annum in general population and generally occurs in women between the ages of 20 and 42 years. LR may precede the onset of stroke by years and the trunk and/or buttocks are involved in nearly all patients. The cerebrovascular manifestations are mostly secondary to ischemia (transient ischemic attacks and cerebral infarct). Other neurological symptoms range from headache, cerebral hemorrhage, seizures, cognitive and psychiatric disturbances. The involved internal organs include heart, kidney, and eyes. Histological findings of skin are characteristic and the involved vessels are small to medium-sized arteries at the border of dermis to subcutis with a distinct histopathological time course. The main diagnostic criteria are general LR with typical histopathological findings on skin biopsy and focal neurological deficits. The pathogenesis is related to hypercoagulable state and intrinsic small-vessel vasculopathy. The optimal management remains an unsolved problem and long-term anticoagulation have been recommended for cerebral ischemic events based on the presumed pathogenesis. There are controversial results in treatment of SS with immunomodulatory agents. The aim of this review is to comprehensively discuss this disease.
Topics: Diagnostic Imaging; Genetic Predisposition to Disease; Global Health; Humans; Morbidity; Sneddon Syndrome
PubMed: 25551694
DOI: 10.1186/s13023-014-0215-4