A child, homozygous for a stop codon in exon 11, shows milder cystic fibrosis symptoms than her heterozygous nephew.

The clinical and molecular findings in an infant with mild manifestations of cystic fibrosis, who is homozygous for the G542X mutation, and her heterozygous nephew, who is severely affected, are described. The major mutation recently identified in the CFTR genel-3 is a specific deletion of three base pairs, which results in the loss of a phenylalanine residue at amino acid position 508 (AF508).3 In a sample of Belgian CF patients, 68-1% of all CF chromosomes (94 out of 138 CF chromosomes) carried this mutation.4 Since then, a series of rarer mutations has been reported (CF genetic analysis consortium, personal communication), including the 2566insAT5 and the G542X mutation (Kerem et al, personal communication). The 2566insAT mutation was not present in our Belgian population sample. In our CF patients, the G542X mutation, in which the glycine (GGA) at amino acid position 542 in exon 11 is mutated to a stop codon (TGA), accounted for 7-3% of the CF chromosomes, being probably the second most frequent CF mutation in this population sample. Here we describe the clinical and molecular findings in a child who is only mildly affected although homozygous for the mutation, and a child who is severely affected and heterozygous for the G542X mutation and a new mutation in exon 9 (G458V).