Three Major Controversies in Neurology: A Debate
Three Major Controversies in Neurology: A Debate
Claes Wahlestedt, MD, PhD, of the University of Miami Miller School of Medicine, responded to Dr Klein by arguing that it's just too early to widely consider exome sequencing in clinical neurology.
Dr Wahlestedt presented three main cautions against adopting the technology too early: (1) Exome sequencing is largely still in the realm of research; (2) there are no first-line tests based on gene sequencing in neurology; and (3) most gene-sequencing findings in neurology—and most of medicine, for that matter—are not actionable.
He also sees the fact that exome sequencing reveals no information about epigenetics or noncoding regions of the genome, which are increasingly being seen as contributing to disease. "Exomes are only 1.5% of the genome—what about the rest of the genome?" Wahlestedt presented data demonstrating that protein-coding regions have been relatively conserved as humans evolved away from other primates, whereas noncoding genes have changed considerably and appear to contribute to numerous disorders not found in other species.
He then supported his stance by reviewing cancer therapeutics: Numerous mutations are linked with specific tumors, yet other than in a few cases—one being certain non-small cell lung cancer subtypes—cancer treatment is still not heavily guided by genomics.
"For research, [sequencing] is highly, highly valuable. But I think that clinical expertise remains paramount—family history, physicals, medical history. For sure, medical geneticists need to know this information. The question is how much a neurologist needs to know."
During the rebuttal, Dr Klein acknowledged that genetic testing is usually not a first-line test and that there often may be other more useful, cheaper tests available. However, she feels there are cases in which genomic sequencing can be useful, including evaluating children in who you may want to avoid unpleasant and invasive procedures like MRIs and lumbar punctures. Klein also sees the fact that exome sequencing doesn't take into account the whole genome as motivation to consider whole-genome testing and optimize technologies that profile epigenetic factors.
Dr Wahlestedt responded by acknowledging that technology has contributed to medicine immensely and that he wants it to continue progressing. "It's amazing what it can do today, but again, most of this is for research...and medical genetics," he commented.
So, per the audience, should whole-exome sequencing be a part of neurology today?
The Consensus: Yes (~60% Yes, 40% No)
Gene Sequencing in Neurology: Nay
Claes Wahlestedt, MD, PhD, of the University of Miami Miller School of Medicine, responded to Dr Klein by arguing that it's just too early to widely consider exome sequencing in clinical neurology.
Dr Wahlestedt presented three main cautions against adopting the technology too early: (1) Exome sequencing is largely still in the realm of research; (2) there are no first-line tests based on gene sequencing in neurology; and (3) most gene-sequencing findings in neurology—and most of medicine, for that matter—are not actionable.
He also sees the fact that exome sequencing reveals no information about epigenetics or noncoding regions of the genome, which are increasingly being seen as contributing to disease. "Exomes are only 1.5% of the genome—what about the rest of the genome?" Wahlestedt presented data demonstrating that protein-coding regions have been relatively conserved as humans evolved away from other primates, whereas noncoding genes have changed considerably and appear to contribute to numerous disorders not found in other species.
He then supported his stance by reviewing cancer therapeutics: Numerous mutations are linked with specific tumors, yet other than in a few cases—one being certain non-small cell lung cancer subtypes—cancer treatment is still not heavily guided by genomics.
"For research, [sequencing] is highly, highly valuable. But I think that clinical expertise remains paramount—family history, physicals, medical history. For sure, medical geneticists need to know this information. The question is how much a neurologist needs to know."
During the rebuttal, Dr Klein acknowledged that genetic testing is usually not a first-line test and that there often may be other more useful, cheaper tests available. However, she feels there are cases in which genomic sequencing can be useful, including evaluating children in who you may want to avoid unpleasant and invasive procedures like MRIs and lumbar punctures. Klein also sees the fact that exome sequencing doesn't take into account the whole genome as motivation to consider whole-genome testing and optimize technologies that profile epigenetic factors.
Dr Wahlestedt responded by acknowledging that technology has contributed to medicine immensely and that he wants it to continue progressing. "It's amazing what it can do today, but again, most of this is for research...and medical genetics," he commented.
So, per the audience, should whole-exome sequencing be a part of neurology today?
The Consensus: Yes (~60% Yes, 40% No)
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