Scientists at Baylor College of Medicine, Baylor Genetics, the University of Texas Health Science Center at Houston and Texas Children\u2019s Hospital are combining descriptions of patients\u2019 clinical features with their complex genetic information in a unified analysis to obtain more precise diagnoses of complex diseases, particularly those that involve more than one gene causing the condition.
\nThe researchers anticipate that improved clinical and genetic diagnoses could lead to patients receiving more effective treatments and families benefiting from needed counselling.
\n\u201cOne of the main interests of our lab is to better understand the impact of genetic variation on human health and disease,\u201d said co-first author Dr. Jennifer Posey, assistant professor of molecular and human genetics at Baylor.
\n\u201cTraditionally, physicians have spoken of a unifying diagnosis, meaning that genetic conditions are due to mutations in only one gene,\u201d said co-first author Dr. Tamar Harel, who was a genetics fellow at Baylor when she was working on this study and currently is a geneticist at Hadassah Medical Center in Israel. \u201cYet, we see here that two or more genes can be involved in a disease and produce a complex clinical picture. For many in the field, this is a revolutionary idea.\u201d <\/p>\n
The challenge of diagnosing diseases with multiple genetic causes<\/strong> Paving a future toward more precise multiple genetic diagnoses <\/strong> Baylor College of Medicine http:\/\/tinyurl.com\/jm44mr5<\/link>\n","protected":false},"excerpt":{"rendered":" Scientists at Baylor College of Medicine, Baylor Genetics, the University of Texas Health Science Center at Houston and Texas Children\u2019s Hospital are combining descriptions of patients\u2019 clinical features with their complex genetic information in a unified analysis to obtain more precise diagnoses of complex diseases, particularly those that involve more than one gene causing the […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"class_list":["post-1136","post","type-post","status-publish","format-standard","hentry","category-e-news"],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1136"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=1136"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1136\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=1136"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=1136"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=1136"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\nThe researchers used whole exome sequencing to analyse all the genes in the genomes of nearly 7,400 unrelated patients with the goal of identifying the genetic cause of their conditions. They found a genetic cause in 2,076 of the 7,374 patients (28 percent); among these patients, 101 (approximately 5 percent) had two or more disease genes involved. If an individual has multiple defective genes, he or she may present with a complex set of clinical features that may lead to an imprecise diagnosis.
\n\u201cClinically, multiple genetic causes can be missed because a patient may present with characteristics that overlap those of two different conditions, so the patient can be diagnosed with one or the other,\u201d said Posey. \u201cAlternatively, a patient\u2019s clinical characteristics may not match those of any described condition, so the patient may be diagnosed with what is thought to be a new condition.\u201d
\n\u201cIn these situations, we, as physicians, have to think of the possibility that more than one gene might be involved in the patient\u2019s disease,\u201d said senior author Dr. James R. Lupski, Cullen Professor of Molecular and Human Genetics at Baylor. \u201cOur study shows the limitations of defining a disease according to what we see in the clinic alone. Our work shows the need to consider that a patient may have two or more genetic diseases, not one, and to send for a genomic test to help sort out the patient\u2019s condition and causes of it.\u201d <\/p>\n
\n\u201cOne of the contributions of our work involves utilization of a structured phenotype ontology,\u201d said Posey. \u201cThis computational tool allows us to model complex clinical features (phenotypes) that can result when more than one gene is involved, in order to better understand, from the perspective of the physician, how such cases may present in the clinic.\u201d
\nFurthermore, Dr. Regis James, now at Regeneron Pharmaceuticals, previously created OMIM Explorer while training as a graduate student at BCM. OMIM Explorer is a tool that helps analyse genomic data in the context of the clinical characteristics of the patient. Both James and his thesis advisor and mentor, Dr. Chad Shaw, director of bioinformatics at Baylor Genetics and associate professor of molecular and human genetics at Baylor, were contributors to this work.
\n\u201cIt provides a more complete perspective of how genes and physical traits relate to each other,\u201d said Lupski.
\n\u201cMy colleagues and I anticipate that in the future, geneticists, clinicians and mathematicians will work together using genetic and clinical information to make diagnostic and therapeutic decisions,\u201d said Harel. <\/p>\n