News
Hattie Yound/Science Photo Library
New cystic fibrosis genetic tests bring hope and dilemmas
Published Online December 13, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70280-7 For more on newborn screening for cystic fibrosis see Lancet Respir Med 2013; 1: 108–09
On Nov 20, 2013, the US Food and Drug Administration approved four new cystic fibrosis (CF) genetic tests. Developed by Illumina (San Diego, CA, USA), these next-generation genetic sequencing tests are intended to quickly and cheaply identify abnormalities in the CF transmembrane conductance regulator (CFTR) gene that can lead to CF. “The type of mutation will help us determine which of some potential new treatments for CF are going to be effective”, said Marlyn Woo, a pulmonologist at the University of California, Los Angeles, and director of the cystic fibrosis clinic at the Children’s Hospital of Los Angeles. The addition of CF testing to newborn screening panels in several states in the USA, as well as the proliferation of genetic sequencing
in general clinical care, has led to an increase in the number of patients with known CFTR mutations. At present, scientists have identified more than 2000 CFTR mutations that vary by ethnic origin. The dilemma for physicians and families alike is that not all CFTR mutations will lead to CF in all patients. Doctors want to follow these patients closely, since early intervention has been linked to better outcomes, but the process is expensive for families, both emotionally and financially. Parents fear that every sniffle means imminent disease. Regular follow-up at specialist clinics can also be extremely costly. But Woo says that the problems created by an increase in genetic testing might also be solved by the
increased use of these tests. As the number of people with various CFTR mutations grows, researchers can more confidently assess whether a particular mutation will lead to CF symptoms. Treatments tailored to specific CFTR mutations have already begun to emerge, and Woo says that more are probably on the way. Nonetheless, genetic tests do not replace the sweat chloride test and other clinical assessments. “Genotyping, in and of itself, does not make a diagnosis. Sending off a CF genotype without a sweat chloride test is not cost-effective. Although the sweat chloride test is still the gold standard, physicians also need to look at the clinical features of the patient to make their diagnosis”, Woo said.
Carrie Arnold
KTS Design/Science Photo Library
Novel gene linked to severe childhood asthma
Published Online December 13, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70279-0 For the study of the genetic background of asthma see Nat Genet 2013; published online May 27. http://dx.doi. org/10.1038/ng.2830
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A novel gene associated with an increased risk of developing severe childhood asthma has been identified, say researchers. Despite asthma exacerbations being among the most common causes of admission to hospital during childhood, there remains a lack of treatment options for preventing and treating exacerbations. In this latest study, an international research team set out to learn more about the genetic background of early childhood asthma with severe exacerbations using a genome-wide association study on DNA obtained from Danish health registries. The investigators compared genomes from 1173 children aged 2–6 years who had been admitted to hospital for asthma with the genomes from a control group of 2522 adults and children without asthma.
Overall, the researchers identified five genes associated with asthma development. Four of these genes, GSDMB, IL33, RAD50, and IL1RL1, have been previously reported, but a novel gene called CDHR3 was identified, which is active in epithelial cells lining the surfaces of airways. The CDHR3 (rs6967330) genotype increased the risk of asthma admissions (hazard ratio [HR] 1·7, 95% CI 1·2–2·4; p=0·002) and severe exacerbations (HR 1·4, 1·1–1·9; p=0·007) in the first 6 years of life compared with the control group. The findings were then replicated using data from 3975 children of both European and non-European ancestry. Norman Edelman, from the American Lung Association (Washington, DC, USA) said that “this study confirms that asthma is
not a single entity but a collection of phenotypes and, now we see, perhaps separate genotypes”. He continues, “there is no doubt that the predisposition to asthma is polygenic in nature. This study discovers a new gene which may be of particular importance in severe asthma”. Gary Ruiz, from the British Lung Foundation (London, UK), added that “CDHR3 is from a family of proteins which help cells in the epithelium interact and keep together. If these cells are abnormal, there may be a greater susceptibility to an exaggerated immune response to triggers from the environment, producing hyper-reactive airways… This could certainly have some implications for our understanding of what causes this type of asthma”.
Sanjay Tanday
www.thelancet.com/respiratory Vol 2 January 2014
Hattie Yound/Science Photo Library
New cystic fibrosis genetic tests bring hope and dilemmas
Published Online December 13, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70280-7 For more on newborn screening for cystic fibrosis see Lancet Respir Med 2013; 1: 108–09
On Nov 20, 2013, the US Food and Drug Administration approved four new cystic fibrosis (CF) genetic tests. Developed by Illumina (San Diego, CA, USA), these next-generation genetic sequencing tests are intended to quickly and cheaply identify abnormalities in the CF transmembrane conductance regulator (CFTR) gene that can lead to CF. “The type of mutation will help us determine which of some potential new treatments for CF are going to be effective”, said Marlyn Woo, a pulmonologist at the University of California, Los Angeles, and director of the cystic fibrosis clinic at the Children’s Hospital of Los Angeles. The addition of CF testing to newborn screening panels in several states in the USA, as well as the proliferation of genetic sequencing
in general clinical care, has led to an increase in the number of patients with known CFTR mutations. At present, scientists have identified more than 2000 CFTR mutations that vary by ethnic origin. The dilemma for physicians and families alike is that not all CFTR mutations will lead to CF in all patients. Doctors want to follow these patients closely, since early intervention has been linked to better outcomes, but the process is expensive for families, both emotionally and financially. Parents fear that every sniffle means imminent disease. Regular follow-up at specialist clinics can also be extremely costly. But Woo says that the problems created by an increase in genetic testing might also be solved by the
increased use of these tests. As the number of people with various CFTR mutations grows, researchers can more confidently assess whether a particular mutation will lead to CF symptoms. Treatments tailored to specific CFTR mutations have already begun to emerge, and Woo says that more are probably on the way. Nonetheless, genetic tests do not replace the sweat chloride test and other clinical assessments. “Genotyping, in and of itself, does not make a diagnosis. Sending off a CF genotype without a sweat chloride test is not cost-effective. Although the sweat chloride test is still the gold standard, physicians also need to look at the clinical features of the patient to make their diagnosis”, Woo said.
Carrie Arnold
KTS Design/Science Photo Library
Novel gene linked to severe childhood asthma
Published Online December 13, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70279-0 For the study of the genetic background of asthma see Nat Genet 2013; published online May 27. http://dx.doi. org/10.1038/ng.2830
30
A novel gene associated with an increased risk of developing severe childhood asthma has been identified, say researchers. Despite asthma exacerbations being among the most common causes of admission to hospital during childhood, there remains a lack of treatment options for preventing and treating exacerbations. In this latest study, an international research team set out to learn more about the genetic background of early childhood asthma with severe exacerbations using a genome-wide association study on DNA obtained from Danish health registries. The investigators compared genomes from 1173 children aged 2–6 years who had been admitted to hospital for asthma with the genomes from a control group of 2522 adults and children without asthma.
Overall, the researchers identified five genes associated with asthma development. Four of these genes, GSDMB, IL33, RAD50, and IL1RL1, have been previously reported, but a novel gene called CDHR3 was identified, which is active in epithelial cells lining the surfaces of airways. The CDHR3 (rs6967330) genotype increased the risk of asthma admissions (hazard ratio [HR] 1·7, 95% CI 1·2–2·4; p=0·002) and severe exacerbations (HR 1·4, 1·1–1·9; p=0·007) in the first 6 years of life compared with the control group. The findings were then replicated using data from 3975 children of both European and non-European ancestry. Norman Edelman, from the American Lung Association (Washington, DC, USA) said that “this study confirms that asthma is
not a single entity but a collection of phenotypes and, now we see, perhaps separate genotypes”. He continues, “there is no doubt that the predisposition to asthma is polygenic in nature. This study discovers a new gene which may be of particular importance in severe asthma”. Gary Ruiz, from the British Lung Foundation (London, UK), added that “CDHR3 is from a family of proteins which help cells in the epithelium interact and keep together. If these cells are abnormal, there may be a greater susceptibility to an exaggerated immune response to triggers from the environment, producing hyper-reactive airways… This could certainly have some implications for our understanding of what causes this type of asthma”.
Sanjay Tanday
www.thelancet.com/respiratory Vol 2 January 2014
