De Braekeleer M, Allard C, Leblanc J P, Simard F, Aubin G
Département des Sciences Humaines Université du Québec à Chicoutimi, Canada.
Hum Genet. 1997 Dec;101(2):208-11. doi: 10.1007/s004390050616.
Cystic fibrosis (CF) has a high incidence in the French-Canadian population of Saguenay Lac-Saint-Jean (Quebec). The A455E mutation accounts for 8.3% of the CF chromosomes. This mutation was shown to be associated with a milder lung disease in the Dutch population. Twenty two CF patients distributed in 17 families and compound heterozygotes for the A455E mutation have been followed at the Clinique de Fibrose Kystique de Chicoutimi. Fourteen patients also carried the delta F508 mutation while the remaining eight patients had the 621 + 1G-->T mutation. Each patient was matched by sex and age to a patient homozygous for the delta F508 mutation. The pairs were analyzed for several clinical and laboratory variables. The A455E compound heterozygotes were diagnosed at a later age (P = 0.003) and had chloride concentrations at the sweat test lower than those homozygous for the delta F508 mutation (P = 0.007). More patients were pancreatic sufficient (P = 0.004). They had a higher Shwachman score (P = 0.001) and better pulmonary function tests (P < 0.02). CF patients compound heterozygous for the A455E mutation have a milder pancreatic and lung disease than the delta F508 homozygotes. Therefore, the A455E should be associated with a better prognosis.
囊性纤维化（CF）在魁北克省萨格奈-圣让湖地区的法裔加拿大人中发病率较高。A455E突变占CF染色体的8.3%。在荷兰人群中，该突变与较轻的肺部疾病相关。希库蒂米囊性纤维化诊所对分布在17个家庭中的22名CF患者以及A455E突变的复合杂合子进行了随访。14名患者还携带ΔF508突变，其余8名患者携带621 + 1G→T突变。每个患者在性别和年龄上与一名ΔF508突变纯合子患者匹配。对这些配对患者的几个临床和实验室变量进行了分析。A455E复合杂合子的诊断年龄较晚（P = 0.003），汗液试验中的氯化物浓度低于ΔF508突变纯合子（P = 0.007）。胰腺功能正常的患者更多（P = 0.004）。他们的施瓦赫曼评分更高（P = 0.001），肺功能测试结果更好（P < 0.02）。A455E突变复合杂合子的CF患者的胰腺和肺部疾病比ΔF508纯合子患者轻。因此，A455E突变可能与更好的预后相关。
