A novel CFTR frame-shift mutation, 935delA, in two Hispanic cystic fibrosis patients.
The currently available mutation analysis panel detects about 50-60% of CFTR mutations in Hispanic patients. In order to search for Hispanic CF mutations, we developed a temporal temperature gradient gel electrophoresis (TTGE) method to screen for unknown mutations. Using TTGE to study the CFTR gene has lead to the discovery of many novel mutations in Hispanic patients. A novel frame-shift mutation, 935delA, was found in two unrelated patients. One was heterozygous for two novel frame-shift mutations, 663delT and 935delA, and the other was heterozygous for DeltaF508 and 935delA. Both patients showed severe phenotype with meconium ileus, pancreatic insufficiency, and early pulmonary microbial colonization with Pseudomonas aeruginosa. Patient 1 died at 4 years of age. Patient 2 had an upper lobectomy. The 935delA mutation produces a truncated polypeptide with only 21% of the full-length protein. The severe course of clinical manifestation is consistent with two oppressively truncated mutant polypeptides encoded by both mutant alleles in patient 1 and the compound heterozygosity truncation and DeltaF508 mutations in patient 2.
Wang
J
J
Institute for Molecular and Human Genetics, Georgetown University Medical Center, M4000, 3800 Reservoir Road, NW, Washington, D.C. 20007, USA.
Bowman
C M
CM
Wong
L J
LJ
D001483:Base Sequence; D003550:Cystic Fibrosis / Q000201:enzymology* / Q000208:ethnology / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D016368:Frameshift Mutation; D006630:Hispanic or Latino; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
C505032:CFTR protein, human; D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator