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Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation
Author(s) -
Varon Raymonda,
Stuhrmann Manfred,
Macek Milan,
Kufardjieva Annie,
Angelicheva Dora,
Magdorf Klaus,
Jordanova Albena,
Savov Alexey,
Wahn Ulrich,
Macek Milan,
Lalov Vesselin,
Ivanova Tanya,
Ellemunter Helmut,
Vavrova Vera,
Ferak Vladimir,
Kayserova Hana,
Reis André,
Kalaydjieva Luba
Publication year - 1995
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380060304
Subject(s) - cystic fibrosis , biology , german , slavic languages , mutation , pulmonary fibrosis , disease , exocrine pancreatic insufficiency , lung disease , medicine , genetics , lung , gene , linguistics , history , classics , philosophy
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 missensemutation 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 ΔF508 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 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. © 1995 Wiley‐Liss, Inc.