Mild pulmonary disease in a cystic fibrosis child homozygous for R553X.

G A T C Nonsense mutations frequently cause severe illness because premature termination of messenger RNA translation usually creates unstable truncated proteins. However, Cutting et al' described two patients carrying nonsense mutations in each cystic fibrosis gene (G542X/ S1255X and R553X/W1316X) with severe pancreatic involvement but mild pulmonary disease. Furthermore, Cuppens et aP and Bonduelle et aP described children homozygous for the G542X stop mutation who were only mildly affected. Recently, Bal et a14 reported a patient homozygous for the R553X nonsense mutation who was moderately severely affected. We present the clinical and molecular findings of a child also homozygous for R553X but with mild pulmonary disease. This boy was born at term in July 1981, birth weight 2500 g, to healthy, unrelated parents of mixed ancestry: the mother of Irish, English/Welsh descent and the father of Welsh and Greek ancestry. Cystic fibrosis (CF) presented neonatally with meconium ileus, which was treated successfully with Gastrographin enemas. CF was confirmed by positive pilocarpine iontophoresis sweat test at four days. Average faecal fat excretion at 6 years was 5-7 g per day (three day collection, patient taking Creon). Conventional treatment for CF has been given. The clinical course has been mild, with no further hospital admissions. A single episode of right middle lobe infection at 5 years resolved with oral antibiotics. Pseudomonas aeruginosa was isolated from sputum cultures soon after this, but not subsequently. Meconium ileus equivalent has occurred in recent years. Liver function tests have remained nor-