ABCMdb

PMID: 7516232

Bienvenu T, Cazeneuve C, Beldjord C, Dusser D, Kaplan JC, Hubert D
A new missense mutation (G27E) in exon 2 of the CFTR gene in a mildly affected cystic fibrosis patient.
Hum Mol Genet. 1994 Feb;3(2):365-6., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Gly27Glu 2 365-366 A new missense mutation (G27E) in exon 2 of the CFTR gene in a mildly affected cystic fibrosis patient Thierry Bienvenu*, Cecile Cazeneuve, Cherlf Beldjord, Daniel Dusser1 , Jean Claude Kaplan and Dominique Hubert1 Laboratoire de Bkxhimie Gen&ique, HOpital Cochin, 123 Bd de Port Royal, 75014 Paris and 1 Service de Pneumotogie, Hopital Cochin, Paris, France Received September 27, 1993; Revised and Accepted December 15, 1993 Cystic Fibrosis (CF) is the most common severe autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2500 live births (1). Login to comment 17 ABCC7 p.Gly27Glu Direct sequencing of this PCR product showed one novel mutation, a missense mutation in exon 2 named G27E (G-A at 212) (Figure lb). Login to comment 19 ABCC7 p.Gln30* ABCC7 p.Gly27Glu ABCC7 p.Gly27Glu ABCC7 p.Gly27Glu We believe that the new missense mutation represents disease-causing mutation because it was not found among more than 100 normal 10% M C N 60% Figure 1. a) Detection of G27E mutation by Denaturing Gradient Gel Electrophoresis: M, G27E, C, control Q30X, N, normal sample b) DNA sequence analysis of the mutation G27E. Login to comment 34 ABCC7 p.Gly27Glu ABCC7 p.Gly27Glu The missense mutation G27E, which results in a glutamic acid for a glycine at position 27, produces very mild symptoms, despite the radical change in amino acid sequence. Login to comment 35 ABCC7 p.Gly85Glu ABCC7 p.Gly91Arg This observation is consistent with the mild clinical phenotype already observed in compound heterozygote patients with another missense mutation in exon 3 (G91R) (13) or in homozygous patient for the G85E mutation (14). Login to comment 36 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347Leu ABCC7 p.Glu92Lys Other missense mutations (i.e. E92K, R117H, R334W, R347P, R347L) especially located in the first transmembrane domain are associated with pancreatic sufficiency (15-17). Login to comment 37 ABCC7 p.Gly27Glu Missense mutations such as this novel mutation G27E that we describe in this report could contribute to the less severe expression of the disease associated with pancreatic sufficiency. Login to comment 38 ABCC7 p.Gly27Glu We must wait the finding of a homozygous patient for G27E to see whether or not it results in a mild phenotype. Login to comment 39 ABCC7 p.Gly27Glu Functional studies of this mutation, regarding the chloride channel activity of CFTR for G27E, should provide further insights about its role in the CF phenotype. Login to comment