McCormick Jonathan, Green Michael W, Mehta Gita, Culross Frank, Mehta Anil
The UK CF Database, Tayside Institute of Child Health, Ninewells Hospital, Dundee DD1 9SY, UK.
Eur J Hum Genet. 2002 Oct;10(10):583-90. doi: 10.1038/sj.ejhg.5200850.
The objective was to determine the composition of the Cystic Fibrosis (CF) Population attending specialist UK CF centres in terms of age, gender, age at diagnosis, genotype and ethnicity. With the planned introduction of the national CF screening programme in the UK, cystic fibrosis transmembrane regulator (CFTR) mutations were compared between different ethnic groups enabling a UK-specific frequency of mutations to be defined. Data were analysed from the patient biographies held in the UK CF Database (see www.cystic-fibrosis.org.uk). The currently registered population of 5,274 CF patients is 96.3% Caucasian with a male preponderance that significantly increases with age. The majority of the 196 non-Caucasian CF patients are from the Indian Subcontinent (ISC), of which one in 84 UK CF patients are of Pakistani origin. The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4). The distribution of Caucasian patients with deltaF508/deltaF508, deltaF508/Other and Other/Other does not fit the expected distribution with a Hardy-Weinberg model unless those patients without a detected mutation are excluded (P<0.001). The UK CF Database has shown the UK CF population to have distinct characteristics separate from the North American and European CF Registries. The ISC group contains many mutations not recognised by current genetic analysis, and one in four ISC patients have no CFTR mutations identified. The CFTR analysis proposed for the screening programme would detect 96% of patients registered in the database, but is unlikely to achieve the desired >80% detection rates in the ethnic minority groups. Screen-positive, non-Caucasian infants without an identifiable CFTR mutation should be referred for a sweat test and genetic counselling when serum trypsinogen concentrations remain elevated after birth.
目的是确定在英国专科囊性纤维化（CF）中心就诊的CF患者群体在年龄、性别、诊断年龄、基因型和种族方面的构成。随着英国全国CF筛查计划的计划推行，对不同种族群体之间的囊性纤维化跨膜传导调节因子（CFTR）突变进行了比较，从而确定了英国特有的突变频率。分析了英国CF数据库（见www.cystic-fibrosis.org.uk）中患者传记的数据。目前登记的5274例CF患者中，96.3%为白种人，男性占优势，且随年龄显著增加。196例非白种人CF患者大多来自印度次大陆（ISC），其中84例英国CF患者中有1例是巴基斯坦裔。最常见的CFTR突变，即ΔF508，在所有CF染色体中占74.1%。在白种人CF患者群体中，57.5%为ΔF508纯合子，但在英国ISC CF患者群体中，只有24.7%，ΔF508纯合子患者明显较少（95%置信区间（CI）0.2 - 0.4）。除非排除未检测到突变的患者，否则携带ΔF508/ΔF508、ΔF508/其他和其他/其他的白种人患者分布不符合哈迪-温伯格模型的预期分布（P<0.001）。英国CF数据库显示，英国CF患者群体具有与北美和欧洲CF注册机构不同的特征。ISC组包含许多当前基因分析未识别的突变，四分之一的ISC患者未检测到CFTR突变。筛查计划提议的CFTR分析将检测到数据库中登记患者的96%，但在少数族裔群体中不太可能达到理想的>80%的检测率。出生后血清胰蛋白酶原浓度持续升高且筛查呈阳性的非白种人婴儿，若未检测到可识别的CFTR突变，应转诊进行汗液试验和遗传咨询。
