A frame-shift mutation in the cystic fibrosis gene

CYSTICfibrosis (CF) is a common recessive lethal genetic disorder, affecting 1 in 1,600 Caucasians1. The disease causes defective regulation of chloride-ion transport in exocrine cells2–5. Although in all CF families the disease is linked to a locus on chromosome 7q31 (refs 6-11), there is clinical heterogeneity in the severity of the disease and the age at which it is diagnosed. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene12–13. A three-nucleotide deletion (δF508) causing the loss of a phenylalanine residue in the tenth exon of the CFTR gene has been found on 70% of CF chromosomes12–14 We have now characterized a CF family in which neither parent of the affected individual carries the common mutation, and identified a two-nucleotide insertion in the CF allele of the mother. The mutation introduces a termination codon in exon 13 of the CFTR gene at residue 821, and is predicted to result in the production of a severely truncated nonfunctional protein.

[1]  L. Tsui,et al.  Erratum: Identification of the Cystic Fibrosis Gene: Genetic Analysis , 1989, Science.

[2]  Charles R.scriver,et al.  The Metabolic basis of inherited disease , 1989 .

[3]  Y. Nakamura,et al.  Refined linkage map of chromosome 7 in the region of the cystic fibrosis gene. , 1988, American journal of human genetics.

[4]  L. Tsui,et al.  Erratum: Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA , 1989, Science.

[5]  L. Tsui,et al.  Identification of the cystic fibrosis gene: chromosome walking and jumping. , 1989, Science.

[6]  X. Estivill,et al.  Isolation of a new DNA marker in linkage disequilibrium with cystic fibrosis, situated between J3.11 (D7S8) and IRP. , 1989, American journal of human genetics.

[7]  M. Dean,et al.  Molecular and genetic analysis of cystic fibrosis. , 1988, Genomics.

[8]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[9]  M. Stutts,et al.  Persistence of abnormal chloride conductance regulation in transformed cystic fibrosis epithelia , 1989, Science.

[10]  Y. Nakamura,et al.  Molecular characterization of a spontaneously generated new allele at a VNTR locus: no exchange of flanking DNA sequence. , 1988, Genomics.

[11]  R. Huganir,et al.  Cl- channels in CF: lack of activation by protein kinase C and cAMP-dependent protein kinase. , 1989, Science.

[12]  L. Tsui,et al.  Cystic Fibrosis Locus Defined by a Genetically Linked Polymorphic Dna Marker Author(s): Lap , 2022 .

[13]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[14]  R. Frizzell.  Cystic Fibrosis: a disease of ion channels? , 1987, Trends in Neurosciences.

[15]  M. Litt,et al.  A hypervariable microsatellite revealed by in vitro amplification of a dinucleotide repeat within the cardiac muscle actin gene. , 1989, American journal of human genetics.

[16]  D. Cooper,et al.  Regional mapping of six cloned DNA sequences on human chromosome 7. , 1986, American journal of human genetics.

[17]  Peter J. Scambler,et al.  Localization of cystic fibrosis locus to human chromosome 7cen–q22 , 1985, Nature.

[18]  F. Collins,et al.  Isolation of additional polymorphic clones from the cystic fibrosis region, using chromosome jumping from D7S8. , 1989, American journal of human genetics.

[19]  J. Rowley,et al.  The human met oncogene is related to the tyrosine kinase oncogenes , 1985, Nature.

[20]  P. A. Sant'agnese,et al.  THE ECCRINE SWEAT DEFECT IN CYSTIC FIBROSIS OF THE PANCREAS (MUCOVISCIDOSIS) , 1962 .

[21]  P. Greengard,et al.  Regulation of chloride channels by protein kinase C in normal and cystic fibrosis airway epithelia. , 1989, Science.

[22]  Michael Dean,et al.  A closely linked genetic marker for cystic fibrosis , 1985, Nature.

[23]  J. Weber,et al.  Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. , 1989, American journal of human genetics.