Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation

✍ Scribed by Raymonda Varon; Manfred Stuhrmann; Milan Macek Jr.; Annie Kufardjieva; Dora Angelicheva; Klaus Magdorf; Albena Jordanova; Alexey Savov; Ulrich Wahn; Milan Macek; Vesselin Lalov; Tanya Ivanova; Helmut Ellemunter; Vera Vavrova; Vladimir Ferak; Hana Kayserova; André Reis; Luba Kalaydjieva

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 644 KB
• Volume: 6
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380060304

✦ Synopsis

Communicated by liirgm Horst

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 heternzygotes with the US08 mutation and had a very mild course of CF, suggesting that R347P, similar to other missense mutations affecting the MSDl 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 p u l m o ~r y 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. 0 1995 Wiev-Lis. Inc.