DF508 and 1154insTC

[ehtansky21]

thank you so much for the reply. My 3 1/2 year old is on enzymes and is not growing as fast as the docs would like, he is on pancreacarb ms 16 x2 at each meal and zantac. No lungs problem yet, but we are just now seeing some congestion (hoping it is a cold, but who knows). My 6 week old was just diagnosed and he is chubby as ever, so no treatment yet.

thanks again,
missa

 

[CFHockeyMom]

1154insTC is a frameshift mutation. Frameshift mutations are ClassI mutations altering the production of the protein. These mutations result in the total or partial absence of the protein. This class includes the nonsense mutations and those that produce a premature stop codon (anomalies of splicing and frameshift mutations). In certain cases the mutated mRNA is unstable and doesn?produce the protein. In other cases, the abnormal protein produced will probably be unstable and degrade rapidly. This is what produces the truncated protein or the protein containing the aberrant sequence (anomalies of splicing or the frame shift). Functionally, these mutants are characterized by a loss of conductance of Cl- channel in the affected epithelia.

 

[CFHockeyMom]

1154insTC is a frameshift mutation. Frameshift mutations are ClassI mutations altering the production of the protein. These mutations result in the total or partial absence of the protein. This class includes the nonsense mutations and those that produce a premature stop codon (anomalies of splicing and frameshift mutations). In certain cases the mutated mRNA is unstable and doesn?produce the protein. In other cases, the abnormal protein produced will probably be unstable and degrade rapidly. This is what produces the truncated protein or the protein containing the aberrant sequence (anomalies of splicing or the frame shift). Functionally, these mutants are characterized by a loss of conductance of Cl- channel in the affected epithelia.

 

[CFHockeyMom]

1154insTC is a frameshift mutation. Frameshift mutations are ClassI mutations altering the production of the protein. These mutations result in the total or partial absence of the protein. This class includes the nonsense mutations and those that produce a premature stop codon (anomalies of splicing and frameshift mutations). In certain cases the mutated mRNA is unstable and doesn?produce the protein. In other cases, the abnormal protein produced will probably be unstable and degrade rapidly. This is what produces the truncated protein or the protein containing the aberrant sequence (anomalies of splicing or the frame shift). Functionally, these mutants are characterized by a loss of conductance of Cl- channel in the affected epithelia.

 

[CFHockeyMom]

1154insTC is a frameshift mutation. Frameshift mutations are ClassI mutations altering the production of the protein. These mutations result in the total or partial absence of the protein. This class includes the nonsense mutations and those that produce a premature stop codon (anomalies of splicing and frameshift mutations). In certain cases the mutated mRNA is unstable and doesn?produce the protein. In other cases, the abnormal protein produced will probably be unstable and degrade rapidly. This is what produces the truncated protein or the protein containing the aberrant sequence (anomalies of splicing or the frame shift). Functionally, these mutants are characterized by a loss of conductance of Cl- channel in the affected epithelia.

 

[CFHockeyMom]

1154insTC is a frameshift mutation. Frameshift mutations are ClassI mutations altering the production of the protein. These mutations result in the total or partial absence of the protein. This class includes the nonsense mutations and those that produce a premature stop codon (anomalies of splicing and frameshift mutations). In certain cases the mutated mRNA is unstable and doesn?produce the protein. In other cases, the abnormal protein produced will probably be unstable and degrade rapidly. This is what produces the truncated protein or the protein containing the aberrant sequence (anomalies of splicing or the frame shift). Functionally, these mutants are characterized by a loss of conductance of Cl- channel in the affected epithelia.

 

[ehtansky21]

claudette,
i understand mostly what you were saying, thank you so much. i am wondering, now, what that means in terms of cf symptoms.
thanks,
missa

 

[ehtansky21]

claudette,
i understand mostly what you were saying, thank you so much. i am wondering, now, what that means in terms of cf symptoms.
thanks,
missa

 

[ehtansky21]

claudette,
i understand mostly what you were saying, thank you so much. i am wondering, now, what that means in terms of cf symptoms.
thanks,
missa

 

[ehtansky21]

claudette,
i understand mostly what you were saying, thank you so much. i am wondering, now, what that means in terms of cf symptoms.
thanks,
missa

 

[ehtansky21]

claudette,
i understand mostly what you were saying, thank you so much. i am wondering, now, what that means in terms of cf symptoms.
thanks,
missa

 

[CFHockeyMom]

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.

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.

Of course, 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. So, the above are simply rules of thumb.

Hope that helps...

 

[CFHockeyMom]

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.

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.

Of course, 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. So, the above are simply rules of thumb.

Hope that helps...

 

[CFHockeyMom]

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.

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.

Of course, 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. So, the above are simply rules of thumb.

Hope that helps...

 

[CFHockeyMom]

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.

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.

Of course, 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. So, the above are simply rules of thumb.

Hope that helps...

 

[CFHockeyMom]

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.

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.

Of course, 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. So, the above are simply rules of thumb.

Hope that helps...