Varon R, Stuhrmann M, Macek M, Kufardjieva A, Angelicheva D, Magdorf K, Jordanova A, Savov A, Wahn U, Macek M
Institute of Human Genetics, Free University, Berlin, Germany.
Hum Mutat. 1995;6(3):219-25. doi: 10.1002/humu.1380060304.
Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) that codes for a cAMP-regulated chloride channel. The R347P is a missense mutation located within the first membrane spanning domain (MSD1) of the CFTR protein. This mutation occurs with an overall worldwide frequency of about 0.2%. The patients, originally described with this mutation were compound heterozygotes with the delta F508 mutation and had a very mild course of CF, suggesting that R347P, similar to other missense mutations affecting the MSD1 domain, causes a mild phenotype. We report here a group of 19 CF patients with the R347P mutation of German, Bulgarian, Czech, and Slovak origin, including two homozygotes. Most patients presented with early disease onset, pancreas insufficiency (PI), and early pulmonary involvement, suggesting that this mutation can lead to a severe course of CF. Most R347P alleles in the group studied share a common polymorphic haplotype. In addition, these analyses gave evidence for recurrence of the mutation in two CF patients of German and Czech origin.
囊性纤维化（CF）由囊性纤维化跨膜传导调节因子（CFTR）基因突变引起，该基因编码一种受环磷酸腺苷（cAMP）调节的氯离子通道。R347P是位于CFTR蛋白第一个跨膜结构域（MSD1）内的错义突变。这种突变在全球的总体发生频率约为0.2%。最初描述的携带这种突变的患者是与ΔF508突变的复合杂合子，CF病程非常轻微，这表明R347P与其他影响MSD1结构域的错义突变一样，会导致轻微的表型。我们在此报告一组19名具有R347P突变的CF患者，他们来自德国、保加利亚、捷克和斯洛伐克，其中包括两名纯合子。大多数患者疾病发病早，有胰腺功能不全（PI）和早期肺部受累，这表明这种突变可导致CF的严重病程。在所研究的群体中，大多数R347P等位基因共享一种常见的多态性单倍型。此外，这些分析证明了该突变在两名德国和捷克裔CF患者中再次出现。
