QJM Advance Access originally published online on September 4, 2009
QJM 2009 102(11):793-798; doi:10.1093/qjmed/hcp120
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Clinical phenotype of cystic fibrosis patients with the G551D mutation
From the 1Regional Adult Cystic Fibrosis Centre, Belfast City Hospital, 2Respiratory Medicine Research Group, Centre for Infection and Immunity, The Queen's University of Belfast, 3Biostatistician, The Northern Ireland Clinical Research Support Centre, The Royal Group of Hospitals and 4Regional Genetics Laboratories, Belfast City Hospital, Belfast, N Ireland, UK.
Address correspondence to J.S. Elborn, Regional Adult Cystic Fibrosis Centre, Belfast City Hospital, Belfast, N Ireland, Antrim BT9 7AB, UK
Received 18 May 2009 and in revised form 4 August 2009
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Abstract |
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Background: Data on whether the phenotype of cystic fibrosis (CF) patients with compound heterozygocity for G551D (Gly551Asp) differs from patients with F508del (Phe508del) homozygous mutations is divergent.
Aim: We hypothesized that CF patients with the G551D mutation would have less severe disease than F508del homozygotes.
Design: We compared the clinical phenotype of adult patients with a G551D mutation with adult patients homozygous for F508del and those with the missense mutation R117H (Arg117His). Compound heterozygotes for the G551D and R117H were analysed separately.
Methods: Data were collected for 101 adult CF patients. Group 1–4 represents in order F508del homozygote patients (n = 61), those with the G551D mutation and a more severe mutation (n = 13), those with R117H mutation and a more severe mutation (n = 23) and also those compound for both the R117H and G551D mutations (n = 4).
Results: Our findings have shown that adult patients with the G551D mutation and a second severe mutation have a milder clinical phenotype than F508del homozygous adult patients. Higher FEV1 and body mass index and less impaired glucose tolerance was demonstrated in the patients with G551D and R117H compared to F508del homozygotes. There was a reduced yearly rate of decline of FEV1 (P < 0.05), infection with Pseudomonas aeruginosa along with reduced burden of care. Compound heterozygosity for G551D and R117H mutations was associated with normal spirometry, body mass index, no chronic infection and no symptoms.
Conclusions: Mutations on different chromosomes are not independent of each other for the overall impact on the amount of functional CFTR. This study suggests that patients with the G551D mutation and a second severe mutation have a milder clinical phenotype than F508del homozygous patients, but the phenotype is not as mild as patients with the R117H mutation.