Fetal bowel hyperechogenicity may indicate mild atypical cystic fibrosis: a case associated with a complex CFTR allele

E ditor -Cystic fibrosis (CF) is an autosomal recessive disorder affecting 1/2500 live births in northern European populations 1 and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. 2 Data accumulated over the past 10 years have produced a remarkable repository of mutations and polymorphisms of the CFTRgene. 3 However, the clinical consequences of many rare mutations are still poorly understood and functional studies are not routinely available. Because of the mutational heterogeneity and the rarity of many mutations, most clinical DNA laboratories offer tests that aim to detect 85-90% of CF alleles, and the systematic, cumbersome analysis of the rest of the gene is performed in selected cases only. The routine DNA analysis showed the presence of the paternal N1303K mutation in both the younger and the older brother.CFTR gene studies were pursued using a DGGE scanning strategy, 8 9 and the maternalCFTR allele was found to carry three missense mutations, D443Y (1459G>T, exon 9), G576A (1859G>C, exon 12), and R668C (2134C>T exon 13), which have each previously been reported in males with CBAVD. 10-12 On further analysis, the complex mutated maternal allele was found in the younger boy. Because of this finding, a sweat test was performed in him which showed a slightly increased chloride concentration (35 mEq/l, with a normal upper limit of 28 mEq/l in this age group).