Novel cystic fibrosis mutation (2215INSG) in two adolescent Taiwanese siblings

Cystic fibrosis (CF) is an autosomal recessive disorder that is rarely foun d in Asians. Only four cases of CF from four different families have been r eported in Taiwan. We report two cases of CF involving two teenage siblings . Both presented with repeated airway infections, poor weight gain, clubbin g of the fingers, hypoxemia, and obstructive ventilatory impairment. Multip le focal bronchiectases and emphysema were demonstrated on high-resolution computed tomography. Sweat chloride concentrations, as measured using the m odified sweat chloride test in a closed space with a heater, were 327 mmol/ L and 276 mmol/L, respectively. To confirm the CF diagnosis, DNA mutation a nalysis was performed. All 27 exons of the CF transmembrane conductance reg ulator (TR) gene and their flanking intron sequences were screened for nucl eotide sequence alterations, and the mutations were then identified by dire ct DNA sequence analysis. Both siblings carried 1898+5G-->T; a mutation pre viously identified in Taiwan. In addition, the mutation analysis identified a new single-base-insertion mutation in exon 13 on the second CFTR allele of these patients. This mutation, named 2215insG, is expected to cause a si gnificant disruption of CFTR function. The 1898+5G-->T/2215insG genotype is thus consistent with the CF diagnosis. A new missense mutation, S895N, in exon 15 of the CFTR gene, which cosegregated with 2215insG, was also identi fied in both of these patients.