MUTATION CHARACTERIZATION OF CFTR GENE IN 206 NORTHERN IRISH CF FAMILIES - 30 MUTATIONS, INCLUDING 2 NOVEL, ACCOUNT FOR SIMILAR-TO-94-PERCENT OF CF CHROMOSOMES

A variety of mutation detection techniques, including restriction endo nuclease digestion, allele specific oligonucleotides, and automated fl uorescent sequencing, were used in the identification of 15 CFTR mutat ions representing 86.7% of CF chromosomes in 206 Northern Irish cystic fibrosis (CF) families, A systematic analysis of the 27 exons and int ron/exon boundaries of the CFTR gene was performed using denaturing gr adient gel electrophoresis (DGGE) in an attempt to characterise the 55 unknown CF mutations in 51 patients. Twenty different mutations were detected by DGGE on 30 chromosomes accounting for a further 7.3% of CF alleles. Fifteen of these mutations had not previously been found in Northern Ireland, and two are novel, M1I(G>T) and V562L. In total, 30 CFTR mutations account for 93.9% of the 412 Northern Irish CF chromoso mes tested. The three major CF mutations in Northern Ireland are Delta F508, G551D, and R117H with respective frequencies of 68.0%, 5.1%, an d 4.1%. The efficacy of the DGGE technique was proven by the detection of 77 out of 77 control variants from all the CFTR exons. DGGE is a h ighly efficient and sensitive method for mutation screening especially in large genes where the mutation spectrum is known to be heterogeneo us. (C) 1996 Wiley-Liss, Inc.