{"id":1426,"date":"2009-12-13T08:37:46","date_gmt":"2009-12-13T08:37:46","guid":{"rendered":"http:\/\/euvolution.com\/futurist-transhuman-news-blog\/long-qt-syndrome-location-matters\/"},"modified":"2009-12-13T08:37:46","modified_gmt":"2009-12-13T08:37:46","slug":"long-qt-syndrome-location-matters","status":"publish","type":"post","link":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/genetic-medicine\/long-qt-syndrome-location-matters.php","title":{"rendered":"Long QT Syndrome, location matters"},"content":{"rendered":"

\"\"<\/a>
I just saw a family who had Long QT with a KCNQ<\/span>1 mutation ripping through them. Which is why I loved this email I received from one of my long time readers the day after I saw them.<\/span><\/span><\/p>


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Closer Look at Genetic Testing in Long-QT syndrome<\/span><\/span><\/a><\/div>

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One of my favorite lines from this paper was<\/span><\/span><\/div>

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\"<\/span><\/span>Nothing tests the tools of clinical risk prediction quite like<\/span><\/span> <\/span><\/span><\/sup>sudden death.\"<\/span><\/span><\/div>

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Ummmm<\/span>......Uh Huh.<\/span><\/span><\/div>

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They go on to say<\/span><\/span><\/div>

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\"The difficulties encountered in the clinical<\/span><\/span> <\/span><\/span><\/sup>application of genetic data, even in inherited conditions such<\/span><\/span> <\/span><\/span><\/sup>as the long-QT syndrome (LQTS<\/span>), in which the transmitted risk<\/span><\/span> <\/span><\/span><\/sup>of sudden death is several hundred-fold greater than that in<\/span><\/span> <\/span><\/span><\/sup>the general population, highlight some of the hurdles that must<\/span><\/span> <\/span><\/span><\/sup>be overcome if DNA diagnosis is ever to transform cardiovascular<\/span><\/span> <\/span><\/span><\/sup>medicine. \"<\/span><\/span><\/div>

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The reader then went on to send me a <\/span><\/span>release from ScienceDaily<\/span><\/span><\/span><\/a><\/div>

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But I should probably give you some background.<\/span><\/span><\/div>

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Long QT syndrome is a condition where the electrical activity in your heart is faulty. In fact, the conduction system has dangerous delays that can lead to dangerous heart rhythms which cause sudden death.<\/span><\/span><\/div>

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It is so serious that in every single patient I see, I ask \"Has anyone in your family died suddenly or in their sleep? Has anyone had any crib death? Any sudden unexplainable car accidents?\"<\/span><\/span><\/div>

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This is my lay screen for Sudden Cardiac Death (SCD<\/span>).<\/span><\/span><\/div>

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Long QT is one of the causes of SCD<\/span>. The rate is about 1 in 2000 or so. In 10% of people roughly, the first symptom is sudden death. This can be due to exertion, stress, auditory triggers.<\/span><\/span><\/div>

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A multicenter<\/span> study was performed to evaluate genetic \"noise\" in 1400 controls and approximately 400 subjects (Far more than the Norovirus<\/span> resistance gene for 22andSerge<\/span><\/a>)<\/span><\/span><\/div>

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What did they find? They found some noise......of course. <\/span><\/span><\/div>
This noise was present in about 4% of controls. This is surprisingly low in my estimate......<\/span><\/span><\/div>

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What else did they find? They found a genotype\/phenotype correlation. Which in Autosomal<\/span> Dominant disease is also no big surprise. Which likely will be augmented with modifier genes.<\/span><\/span><\/div>

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What is the \"noise rate\" for other genes? That, my friend is a good question. <\/span><\/span><\/div>

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What is noise? It could be anything we haven't classified as for certain pathogenic or benign. For BRCA<\/span> we call these changes \"Variants of Uncertain Significance\" or affectionately known as VUSes<\/span><\/span><\/span><\/div>

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The VUS<\/span> rate for BRCA<\/span> is anywhere between 10 and 15 percent. Which is why I was so surprised about the LQTS<\/span> study. <\/span><\/span>Heck, there are more than 2 genes involved in LQTS<\/span><\/span><\/span><\/a><\/div>

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So why is this noise such a big deal? As we reach the precipitously dropping cost of the genome, we will be able to have a whole bunch of noise......<\/span><\/span><\/div>

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In fact, I think it will take us at least 20 years to sort out that noise. Add on layers of epigenetics<\/span> and we may have another 20 years.......<\/span><\/span><\/div>

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Why so glum? We do have pretty valid clinical testing for Sudden Cardiac Death. It works, MOST of the time. Whole Genome Scanning?<\/span><\/span><\/div>

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Well, that may be a different story. I have harped on the<\/span><\/span> Incidentalome<\/span><\/span><\/span><\/a> several times on the blog, but this bears repeating.........<\/span><\/span><\/div>

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\"<\/span><\/span> If practitioners pursue these unexpected <\/span><\/span><\/sup>genomic findings without thought, there may be disastrous consequences.<\/span><\/span> <\/span><\/span><\/sup>First, physicians will be overwhelmed by the complexity of pursuing<\/span><\/span> <\/span><\/span><\/sup>unexpected genomic measurements. Second, patients will be subjected<\/span><\/span> <\/span><\/span><\/sup>to unnecessary follow-up tests, causing additional morbidity.<\/span><\/span> <\/span><\/span><\/sup>Third, the cost of genomic medicine will increase substantially<\/span><\/span> <\/span><\/span><\/sup>with little benefit to patients or physicians (but with great<\/span><\/span> <\/span><\/span><\/sup>financial benefits to the genomic testing industry), \"<\/span><\/span><\/div>

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-Zak Kohane<\/span><\/span><\/span><\/div>

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\"Mathematicians<\/span> modeled sequencing the whole genome. As they get up to sequencing 10.000 people they find that the fraction of the population with a false positive result skyrockets up to 60%. What does this<\/span> mean? Well, we have to carefully select who we test. Or better yet we need an immense database of \"Normal Variants\". At a minimum we will need 1000s of \"sequence specialists\" or \"computer sequence analysis programs\" to evaluate and decide if the \"work up\" is indicated or not. Personal Genomics<\/span> is very complex, even more than personalized medicine.\"<\/span><\/span><\/div>

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-Steven Murphy in 2007<\/span><\/span><\/div>

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The Sherpa Says: In Genomics<\/span>, there is going to be a whole lotta<\/span> maybes........which in case you are curious, computers handle very poorly....<\/span><\/b><\/span><\/span><\/div>
\"\"<\/div>","protected":false},"excerpt":{"rendered":"

I just saw a family who had Long QT with a KCNQ1 mutation ripping through them. Which is why I loved this email I received from one of my long time readers the day after I saw them.Closer Look at … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"limit_modified_date":"","last_modified_date":"","_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[5],"tags":[],"class_list":["post-1426","post","type-post","status-publish","format-standard","hentry","category-genetic-medicine"],"modified_by":null,"_links":{"self":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/1426"}],"collection":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/comments?post=1426"}],"version-history":[{"count":0,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/1426\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/media?parent=1426"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/categories?post=1426"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/tags?post=1426"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}