Variant "CFTR:c.443T>A(p.Ile148Asn)"
Search results: 3 records
Variant information
Gene:
CFTR 
Variant:
CFTR:c.443T>A(p.Ile148Asn) 
Genomic location:
chr7:117171122(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_000492.3:c.443T>A(p.Ile148Asn)
Alias:
CFTR:rs35516286 
dbSNP ID:
rs35516286  
GWAS trait:
no data 
Modifier statisitcs
Record:
3 
Disorder:
1 
Reference:
3 
Effect type:
Expressivity(3)  
Modifier effect:
Risk factor(2) ,Altered onset time and altered severity(1)  
Details：
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=0.0014 
    Effect:
    It is concluded that I148T occurs on at least three haplotypes and the complex allele I148T + 9T + 3199del6 is associated with a classic CF phenotype.
    Alias in reference:
    CFTR:c.443T>A(p.Ile148Asn)
    Reference:
    PMID12394343
    Title:
    The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis.
    Species studied:
    Human
    Abstract:
    To determine whether intragenic changes modulate the cystic fibrosis (CF) phenotype in individuals who are positive for the I148T allele.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    Phenotype modifier
    Alias in reference:
    CFTR:rs35516286
    Reference:
    PMID1284534
    Title:
    Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the Cystic Fibrosis Genetic Analysis Consortium.
    Species studied:
    Human
    Abstract:
    Cystic fibrosis is the most common autosomal disorder in the Caucasian population. Since the description of the major mutation of this disease in 1989, over 150 of additional mutations have been identified in the CFTR gene. This update summarizes the different mutations identified and reported before March 15 by members of the international Cystic Fibrosis Genetic Analysis Consortium. The report includes information on DNA sequence variations found in the gene.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time and altered severity 
    Evidence:
    Assessment of genotype–phenotype associations, P=0.002 
    Effect:
    Residual anion secretion was detected in 40% of CF patients, and was associated with later disease onset (P < 0.0001), higher frequency of PS (P < 0.0001), and less severe lung disease (P < 0.05).
    Alias in reference:
    CFTR:rs35516286
    Reference:
    PMID15480987
    Title:
    CFTR Cl- channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    BACKGROUND & AIMS:Cystic fibrosis (CF) is caused by over 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and presents with a widely variable phenotype. Genotype-phenotype studies identified CFTR mutations that were associated with pancreatic sufficiency (PS). Residual Cl- channel function was shown for selected PS mutations in heterologous cells. However, the functional consequences of most CFTR mutations in native epithelia are not well established.METHODS:To elucidate the relationships between epithelial CFTR function, CFTR genotype, and patient phenotype, we measured cyclic adenosine monophosphate (cAMP)-mediated Cl- secretion in rectal biopsy specimens from 45 CF patients who had at least 1 non-DeltaF508 mutation carrying a wide spectrum of CFTR mutations. We compared CFTR genotypes and clinical manifestations of CF patients who expressed residual CFTR-mediated Cl- secretion with patients in whom Cl- secretion was absent.RESULTS:Residual anion secretion was detected in 40% of CF patients, and was associated with later disease onset (P < 0.0001), higher frequency of PS (P < 0.0001), and less severe lung disease (P < 0.05). Clinical outcomes correlated with the magnitude of residual CFTR activity, which was in the range of approximately 12%-54% of controls.CONCLUSIONS:Specific CFTR mutations confer residual CFTR function to rectal epithelia, which is related closely to a mild disease phenotype. Quantification of rectal CFTR-mediated Cl- secretion may be a sensitive test to predict the prognosis of CF disease and identify CF patients who would benefit from therapeutic strategies that would increase residual CFTR activity.