I am currently expecting a CF child. Does anyone out there know some one/ have a child with/ or even have themselves the combination of A455E and DF508? I spoke to a genetic counselor and the only information they could provide to me was a study done in 1995 that compared CF individuals with A455E/DF508 with homozyous DF508. Does anyone have any insight as to what to expect with a A455E/DF508 combination?
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Expecting a CF Child
- Thread starter LauraWoje
- Start date
I am currently expecting a CF child. Does anyone out there know some one/ have a child with/ or even have themselves the combination of A455E and DF508? I spoke to a genetic counselor and the only information they could provide to me was a study done in 1995 that compared CF individuals with A455E/DF508 with homozyous DF508. Does anyone have any insight as to what to expect with a A455E/DF508 combination?
I am currently expecting a CF child. Does anyone out there know some one/ have a child with/ or even have themselves the combination of A455E and DF508? I spoke to a genetic counselor and the only information they could provide to me was a study done in 1995 that compared CF individuals with A455E/DF508 with homozyous DF508. Does anyone have any insight as to what to expect with a A455E/DF508 combination?
I am currently expecting a CF child. Does anyone out there know some one/ have a child with/ or even have themselves the combination of A455E and DF508? I spoke to a genetic counselor and the only information they could provide to me was a study done in 1995 that compared CF individuals with A455E/DF508 with homozyous DF508. Does anyone have any insight as to what to expect with a A455E/DF508 combination?
I am currently expecting a CF child. Does anyone out there know some one/ have a child with/ or even have themselves the combination of A455E and DF508? I spoke to a genetic counselor and the only information they could provide to me was a study done in 1995 that compared CF individuals with A455E/DF508 with homozyous DF508. Does anyone have any insight as to what to expect with a A455E/DF508 combination?
Just a head's up - there are many CFer's with the same 2 gene mutations but their clinical outcomes vary widely. A great example is siblings (with the same two parents) who have CF that varies widely in severity.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Just a head's up - there are many CFer's with the same 2 gene mutations but their clinical outcomes vary widely. A great example is siblings (with the same two parents) who have CF that varies widely in severity.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Just a head's up - there are many CFer's with the same 2 gene mutations but their clinical outcomes vary widely. A great example is siblings (with the same two parents) who have CF that varies widely in severity.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Just a head's up - there are many CFer's with the same 2 gene mutations but their clinical outcomes vary widely. A great example is siblings (with the same two parents) who have CF that varies widely in severity.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Just a head's up - there are many CFer's with the same 2 gene mutations but their clinical outcomes vary widely. A great example is siblings (with the same two parents) who have CF that varies widely in severity.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
Modifier genes, preventative treatment, environment, compliance to medication all play in to clinical outcomes of CF.
CFHockeyMom
New member
DF508 is a Class II gene and A455E is a Class V gene.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
CFHockeyMom
New member
DF508 is a Class II gene and A455E is a Class V gene.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
CFHockeyMom
New member
DF508 is a Class II gene and A455E is a Class V gene.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
CFHockeyMom
New member
DF508 is a Class II gene and A455E is a Class V gene.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
CFHockeyMom
New member
DF508 is a Class II gene and A455E is a Class V gene.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
Class II mutations complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive.
Class V mutations result in significantly decreased production of normal CFTR.
1: Thorax. 2005 Jul;60(7):558-63. Links
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
As NoExcuses said, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome.
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>CFHockeyMom</b></i>
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote></div>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote></div>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>CFHockeyMom</b></i>
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote></div>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote></div>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>CFHockeyMom</b></i>
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote></div>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote></div>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>CFHockeyMom</b></i>
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>CFHockeyMom</b></i>
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)
In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome. </end quote>
This statement has been quoted by our doctor as well... people with a class 2 and a class 4 or 5, (generally speaking) have a fewer complications - better health.
My kids are a class 2 with a class 4 (if I remember correctly)