Tag Archives: L161240

Before two decades the number of genes recognized to have a

Before two decades the number of genes recognized to have a role in the epilepsies has dramatically increased. the growing L161240 importance of educating physicians about when and how to test individuals the need to ensure that affected individuals and their families can make educated choices about screening and get support after receiving the results and the query of what the positive and negative consequences of genetic L161240 testing will become for affected individuals their family members and society. Intro The availability of medical genetic screening in the epilepsies offers increased dramatically because of rapid progress in identifying the causative mutations (discussed in another article in this problem) 1 as well as improvements in laboratory techniques.2-8 In addition to traditional Sanger sequencing which is used to identify mutations in individual genes linked to epilepsy and related disorders clinicians are now presented with an expanded repertoire of screening modalities (Table 1). Chromosomal microarray analysis (CMA) is now often the 1st genetic evaluation carried out in individuals with epilepsy and provides information about chromosomal aneuploidies previously recognized by high-resolution karyotyping as well as about smaller deletions and duplications. Table 1 Clinically available genetic screening modalities in epilepsy Epilepsy-specific gene panels have become available to test for sequence variants and whole L161240 or partial gene deletions and duplications in multiple genes. Currently available panels can simultaneously screen many potentially relevant genes and don’t require the same degree of pretest correlation of genotype to phenotype as is needed for selection of a single-gene test. These panels also have the advantage of being able to detect intragenic deletions that are below the resolution of CMA and might also be missed by Sanger sequencing (heterozygous deletion of one or more exons of a gene cannot be recognized using the Sanger method because the remaining normal copy of those exons provides a normal sequencing result). Whole-exome sequencing (WES) is also clinically available and may provide information about putative pathogenic variants-not only in genes already known to be related to a specific epilepsy syndrome but also in genes that might not be expected to harbour mutations particularly if the epilepsy phenotype differs from that previously observed to be associated with the variant in question.9-11 When applied to a trio (the patient and both biological parents) WES provides an efficient approach to the finding of both and inherited mutations in the coding portions of most genes in the human being genome. Whole-genome sequencing (WGS) which is definitely widely performed in the research setting will probably also shortly be available in the medical center and will provide a means to assay both point mutations and copy number variations across the whole genome.12 In this article we discuss these developments and focus on new issues that they bring to light particularly those related to the benefits and risks of screening and difficulties for the provision of genetic solutions (Package L161240 1). Genetic screening in the epilepsies has the potential to revolutionize the care of affected individuals but to ensure services F2rl1 are delivered in the most effective sensitive and equitable manner possible we need to devote attention to the challenges involved and establish mechanisms to address them. Package 1 Questions raised by the introduction of genetic screening in the epilepsies Informed choiceWhat methods are needed to empower individuals to make an informed choice about whether or not to be tested? Interpreting resultsWhat methods are needed to help individuals and family members comprehend and deal with the results? ImpactWhat are the positive and negative short-term and long-term effects on an affected individual of receiving a genetic analysis? Will unaffected family members choose to learn their genetic status and if so how will this influence their lives? How does the effect of testing relate to specific medical features of epilepsy (such as child years versus adult onset severity and connected intellectual disability)? Incidental findingsWhat should be done to deal with the possibility.