RESUMO
SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients.
Assuntos
Ansiedade/genética , Transtorno do Espectro Autista/genética , Metilação de DNA , Epilepsia/genética , Histona-Lisina N-Metiltransferase/genética , Deficiência Intelectual/genética , Mutação com Perda de Função , Adolescente , Adulto , Criança , Pré-Escolar , Ilhas de CpG , Epigênese Genética , Proteínas F-Box/genética , Feminino , Marcadores Genéticos , Humanos , Recém-Nascido , Histona Desmetilases com o Domínio Jumonji/genética , MasculinoRESUMO
Zellweger spectrum disorder, resulting from mutations in the peroxisome assembly mechanism, is genetically heterogeneous and phenotypically varied in disease characteristics and severity. In addition to manifesting gyration anomalies, affected individuals typically have white matter abnormalities ranging from hypomyelination in infancy to a more diffuse demyelinating leukoencephalopathy pattern in those surviving into childhood. Here we report a unique presentation in a 2/-year-boy with acute neurological deterioration and MRI demonstrating avid contrast enhancement suggesting inflammatory demyelination in the brainstem.