Genotype/Phenotype Association in Cystic Fibrosis: Analyses of the ΔF508, R553X, and 3905insT Mutations
Genotype/Phenotype Association in Cystic Fibrosis: Analyses of the ΔF508, R553X, and 3905insT Mutations
复制标题
囊性纤维化的基因型/表型关联：ΔF508、R553X 和 3905insT 突变的分析
作者：
S. Liechti‐Gallati;Irene Bonsall;N. Malik;V. Schneider;L. Kraemer;A. Ruedeberg;H. Moser;R. Kraemer
摘要：囊性纤维化的一个显著临床现象是病变表现的异质性。因此，必须假设与囊性纤维化相关的突变的性质可能部分决定了表型表现。对45例ΔF508纯合子(ΔF2)、12例ΔF508/R553X复合杂合子(ΔF1/RX1)、3例R553X纯合子(RX2)和13例ΔF508/3905insT复合杂合子(ΔF16)患者的囊性纤维化突变与临床参数的关系进行了研究。我们发现基因定义的亚组在平均发病年龄、慢性铜绿假单胞菌定植的累积发生率和克里斯平-诺曼X射线评分方面存在显著差异。显著的结果以及与相对体重不足有关的一些趋势表明，与ΔF508纯合子相比，R553X杂合子的临床病程较轻，而ΔF16组的疾病更严重。3例R553X纯合子患者在感染铜绿假单胞菌前表现为两个阶段的病程，表现为轻微的进展，而在12岁时定植于铜绿假单胞菌后表现为与ΔF16一样严重的病程。然而，遗传同质性亚组内的广泛差异表明，临床状态的其他决定因素确实存在。
ABSTRACT: A striking clinical phenomenon of cystic fibrosis is the heterogeneous disease expression. It must therefore be assumed that the nature of the mutations associated with cystic fibrosis might partly determine the phenotypic manifestations. The relation between the cystic fibrosis mutations ΔF508, R553X, and 3905insT and clinical parameters such as sweat test electrolytes, age at chronic Pseudomonas aeruginosa colonization, Chrispin-Norman x-ray scores, and relative underweight have been investigated in 45 patients homozygous for ΔF508 (ΔF2), in 12 compound heterozygotes for ΔF508/R553X (ΔF1/ RX1), in three R553X homozygotes (RX2), and in 13 patients compound heterozygous for ΔF508/3905insT (ΔF16). We have found significant differences between the genetically defined subgroups concerning the mean age at onset and the cumulative incidence of chronic P. aeruginosa colonization and Chrispin-Norman x-ray scores. The significant results as well as some trends regarding the relative underweight demonstrate a milder clinical course in R553X heterozygotes and more severe disease in the ΔF16 group compared to ΔF508 homozygotes. The three patients homozygous for R553X presented with a two-stage course showing mild progression before P. aeruginosa infection and as severe a course as the ΔF16 patients after P. aeruginosa colonization at the age of 12 y. The findings presented here indicate that specific mutations can influence the severity and progression of the disease, implicating the importance of mutation and haplotype analyses. However, wide variations within the genetically homogeneous subgroups illustrate that other determinants of the clinical status do exist.
使用 D7S8 的染色体跳跃从囊性纤维化区域分离额外的多态性克隆。
影响因子：
9.8
作者：
Iannuzzi,MC;Dean,M;Drumm,ML;Hidaka,N;Cole,JL;Perry,A;Stewart,C;Gerrard,B;Collins,FS
通讯作者：
Collins,FS