Genotype-phenotype correlations in cystic fibrosis: clinical severity of mutation S549R(T-->G).
With a view to assessing genotype-to-phenotype correlations in cystic fibrosis (CF), the clinical presentation of CF children from the United Arab Emirates (UAE) who were homozygous for cystic fibrosis transmembrane conductance regulator (CFTR) mutation S549R(T-->G was investigated. This mutation is localized in intron 11 (nucleotide binding domain 1 of the CFTR protein) and had so far been described as a private mutation only. The associations between the R549/R549 genotype and 20 outcome variables, including age at diagnosis, sweat chloride concentrations, growth percentiles, meconium ileus, pancreatic sufficiency, pulmonary disease, associated complications and micro-organism colonization were examined in a group of 15 CF children (9 females and 6 males). Mean current age and age at diagnosis were both low (5.4+/-3.5 and 1.0+/-1.1 yrs, respectively). Although none of the 15 CF patients had presented with meconium ileus at birth, all were pancreatic insufficient and had very severe lung disease, with a high rate of Pseudomonas aeruginosa and Staphylococcus aureus. Two patients died during the course of this investigation (one was 5 months and the other, 6 yrs old). The clinical presentation associated with S549R(T-->G) homozygosity in the United Arab Emirates is quite homogeneous and shows an extreme degree and course of cystic fibrosis severity.
Frossard
P M
PM
Dept of Pathology, Faculty of Medicine & Health Sciences, Tawam Hospital, Al Ain, United Arab Emirates.
Hertecant
J
J
Bossaert
Y
Y
Dawson
K P
KP
D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005838:Genotype; D006147:Guanine; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D013941:Thymine
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006147:Guanine; D013941:Thymine