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DF508 is a Class II type gene while 3659delC (frameshift) is a Class I type gene.
Class 1: 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 doesnít 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.
Class 2: mutations altering the cellular maturation of the protein. A number of mutations alter the maturation of the protein and thus the transport of these proteins to the plasma membrane. In this way, the protein is either absent from the plasma membrane or present in a very small quantity. The mutations of this class represent the majority of CF alleles (DF508).
DF508 as you probably know is the most common gene. 3659delC is also pretty common as it is included in the standard panel.
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.
As you know, specific gene types don't guarantee the severity of the disease or the progression however, the info can be referred to as a "rule of thumb". Environment, treatment quality, and treatment compliance are equally important in determining long term prognosis. Afterall, we have many people on the boards (including siblings) with the same genes and very different clinical outcomes.
Class 1: 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 doesnít 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.
Class 2: mutations altering the cellular maturation of the protein. A number of mutations alter the maturation of the protein and thus the transport of these proteins to the plasma membrane. In this way, the protein is either absent from the plasma membrane or present in a very small quantity. The mutations of this class represent the majority of CF alleles (DF508).
DF508 as you probably know is the most common gene. 3659delC is also pretty common as it is included in the standard panel.
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.
As you know, specific gene types don't guarantee the severity of the disease or the progression however, the info can be referred to as a "rule of thumb". Environment, treatment quality, and treatment compliance are equally important in determining long term prognosis. Afterall, we have many people on the boards (including siblings) with the same genes and very different clinical outcomes.