Low segregation ratios in autosomal recessive disorders.

ing from Murcia, Spain. She was born in 1987, without meconium ileus, and was diagnosed as having cystic fibrosis at the age of 5 months, on the basis of growth retardation, gastrointestinal problems (especially diarrhoea and steatorrhoea), and repeated bronchitis. Staphylococcus aureus then Pseudomonas aeruginosa have been found in the patient's sputum since she was 6 months old. She is treated with pancreatic enzymes and antibiotics, but her obstructive lung disease has increased and the patient is classified as severely affected by the clinicians. Using the SSCP technique" to study the DNA extracted from the patient and her family, we detected then identified the stop mutation G542X in the two CFTR genes transmitted to the affected child. This mutation is associated with haplotype 1121221 on the paternal chromosome, and with haplotype 1221221 on the maternal chromosome, as defined by the markers met D/TaqI, met H/TaqI, G2/XbaI, XV2C/TaqI, KM19/ PstI, D9/MspI, and J3.1 I/MspI. The stop mutation G542X is predicted to result in decreased levels of mutant messenger RNA"2 and in a truncated CFTR protein from NBD-1,' suppressing 63% of the molecule. However, the homozygous patients for G542X previously reported had mild pulmonary disease,""5'° which would imply alternative splicing mechanisms suppressing the effect of the stop mutation in some tissues. Contrasting with these reports, we present the second case of a child homozygous for G542X with severe pancreatic and lung disease. Another similar finding has just been reported in a Turkish boy in the neonatal period by Bienvenu et al. "3 Such contradictions in genotype/phenotype correlations might be resolved in the future bymRNA and protein expression studies in target tissues.