SEVERITY OF CYSTIC-FIBROSIS IN PATIENTS HOMOZYGOUS AND HETEROZYGOUS FOR DELTA-F508 MUTATION
SEVERITY OF CYSTIC-FIBROSIS IN PATIENTS HOMOZYGOUS AND HETEROZYGOUS FOR DELTA-F508 MUTATION
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DOI：
10.1016/0140-6736(91)92449-c
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发表时间：
1991-03-16
期刊：
影响因子：
168.9
通讯作者：
SCHWARTZ, M
中科院分区：
文献类型：
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作者：
JOHANSEN, HK;NIR, M;SCHWARTZ, M
为了评估囊性纤维化（CF）的基因型与疾病严重程度之间的关系，研究了在丹麦CF中心就诊的235例患者中其表型表达的几个特征的频率和程度，排除了14例不定期就诊的患者和3例完全不携带DELTA-F508突变的患者。对其余218例患者（年龄4个月至41岁）的病例报告进行仔细评估，并对他们进行DELTA-F508突变分析。DELTA-F508纯合子172个（79%），杂合子46个（20%）。因此，这种突变发生在89%的被分析染色体上。纯合子组和杂合子组在出生时便性肠梗阻、肝脏受累或慢性铜绿假单胞菌感染的比例上没有显著差异。然而，纯合子患者在6个月前出现症状的比例显著高于纯合子患者（p < 0.025）；他们在诊断时（p = 0.013）和转诊时（p = 0.006）明显更年轻；他们需要更多的胰腺酶替代（p = 0.0002），肺功能较差；计算的慢性铜绿假单胞菌年感染率和年死亡率均高于杂合子组（p = 0.0001）。
To assess the relation between genotype and severity of disease in cystic fibrosis (CF) the frequencies and extent of several features of its phenotypic expression were investigated in the 235 patients who attend the Danish CF Centre. 14 patients who attend irregularly and 3 who do not carry the DELTA-F508 mutation at all were excluded. The case-reports of the remaining 218 patients (aged 4 months to 41 years) were carefully evaluated, and they were all analysed for the DELTA-F508 mutation. 172 (79%) were homozygous for DELTA-F508 and 46 (20%) were heterozygous. The mutation therefore occurs on 89% of the chromosomes analysed. There were no significant differences between the homozygous and heterozygous groups in the proportions with meconium ileus at birth, liver involvement, or chronic Pseudomonas aeruginosa infection. However, significantly more of the homozygous patients had onset of symptoms before the age of 6 months (p < 0.025); they were significantly younger at diagnosis (p = 0.013) and centre referral (p = 0.006); they required greater pancreatic enzyme substitution (p = 0.0002) and had poorer lung function; and the calculated yearly incidence of chronic Ps aeruginosa infection and yearly mortality rates were greater than in heterozygous patients (p = 0.0001).