RESUMO
INTRODUCTION: Long-read whole genome sequencing like Oxford Nanopore Technology, is increasingly being introduced in clinical settings. With its ability to simultaneously call sequence variation and DNA modifications including 5-methylcytosine, nanopore is a promising technology to improve diagnostics of imprinting disorders. METHODS: Currently, no tools to analyze DNA methylation patterns at known clinically relevant imprinted regions are available. Here we present NanoImprint, which generates an easily interpretable report, based on long-read nanopore sequencing, to use for identifying clinical relevant abnormalities in methylation levels at 14 imprinted regions and diagnosis of common imprinting disorders. RESULTS AND CONCLUSION: NanoImprint outputs a summarizing table and visualization plots displays methylation frequency (%) and chromosomal positions for all regions, with phased data color-coded for the two alleles. We demonstrate the utility of NanoImprint using three imprinting disorder samples from patients with Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS) and Prader-Willi syndrome (PWS). NanoImprint script is available from https://github.com/carolinehey/NanoImprint.
Assuntos
Síndrome de Angelman , Síndrome de Beckwith-Wiedemann , Metilação de DNA , Sequenciamento por Nanoporos , Síndrome de Prader-Willi , Humanos , Síndrome de Angelman/genética , Síndrome de Angelman/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/diagnóstico , Sequenciamento por Nanoporos/métodos , Nanoporos , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/diagnóstico , Análise de Sequência de DNA/métodosRESUMO
In case of a cerebral abscess without known cause, Pulmonary arteriovenous malformations (PAVM) screening should be performed. If PAVM(s) is identified, Hereditary hemorrhagic telangiectasia (HHT) is very likely and should always be considered. This case shows the benefit of familial screening for HHT and PAVM.