ABCMdb

PMID: 8818956

Tebbutt SJ, Harris A, Hill DF
An ovine CFTR variant as a putative cystic fibrosis causing mutation.
J Med Genet. 1996 Jul;33(7):623-4., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Arg297Gln The equivalent R297Q mutation in exon 7 of the human CFTR gene has been reported in a CF patient. Login to comment 6 ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln However, only a few mutations A B C B C D CD (Io mo0 E eD 1J -T E F G H J K =_ Wild type A to T il1200) _ G to A lO19) R297Q SSCP 3"_-d<303 bp I_ l8*4bo_ di ges l *~~~~~~~~~84bo Figure 1 Pedigree structure of sheep carrying the Gl019A (R297Q) CFTR exon 7 gene variant in the heterozygote state (also a silent polymorphism, A1200T, unpublished data). Login to comment 15 ABCC7 p.Arg297Gln Ewe "G" is heterozygous for the R297Q variant. Login to comment 24 ABCC7 p.Arg297Gln DNA sequence analysis was used to confirm that the R297Q allele is efficiently transcribed (fig 2). Login to comment 25 ABCC7 p.Arg297Gln DNA sequence analysis was used to confirm that the R297Q allele is efficiently transcribed (fig 2). Login to comment 26 ABCC7 p.Arg297Gln This is homologous to a putative cystic fibrosis causing mutation (R297Q) reported in a Northern Ireland family.9 Interestingly, the arginine (R297) residue lies in the first membrane spanning domain of the predicted CFTR protein, specifically part of the cytoplasmic loop between the putative transmembrane helices 4 and 5.1 The threonine-arginine-lysine (TRK) peptide in this region is entirely conserved in the predicted polypeptides from all animal species in which the CFTR gene has been characterised,'0 including human, sheep, cattle, mouse, Xenopus, and dogfish. Login to comment 27 ABCC7 p.Arg297Gln This is homologous to a putative cystic fibrosis causing mutation (R297Q) reported in a Northern Ireland family.9 Interestingly, the arginine (R297) residue lies in the first membrane spanning domain of the predicted CFTR protein, specifically part of the cytoplasmic loop between the putative transmembrane helices 4 and 5.1 The threonine-arginine-lysine (TRK) peptide in this region is entirely conserved in the predicted polypeptides from all animal species in which the CFTR gene has been characterised,'0 including human, sheep, cattle, mouse, Xenopus, and dogfish. Login to comment 28 ABCC7 p.Arg297Gln The two human CF patients reported to carry the R297Q mutation were aged 6 and 8 years (in 1991). Login to comment 29 ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln Clinically, both patients were similarly affected with mild to moderate chest symptoms and both were receiving pancreatic - enzyme supplements.9 A recent study of a French CF family" has suggested that R297Q represents a rare polymorphism, rather than a disease causing mutation, or that the length of a T tract in intron 8 may play a role in influencing the severity ofthe R297Q allele. Login to comment 30 ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln Clinically, both patients were similarly affected with mild to moderate chest symptoms and both were receiving pancreatic - enzyme supplements.9 A recent study of a French CF family" has suggested that R297Q represents a rare polymorphism, rather than a disease causing mutation, or that the length of a T tract in intron 8 may play a role in influencing the severity ofthe R297Q allele. Login to comment 31 ABCC7 p.Arg297Gln At present, it is uncertain if R297Q is a disease causing mutation. Login to comment 32 ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln Nevertheless, if R297Q in the human CFTR protein does indeed contribute to the cystic fibrosis phenotype, it is tempting to consider that an- ^*K'" other animal species, carrying R297Q in the homozygous state, might also show some of -'('- the symptoms of CF. Login to comment 33 ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln The ewe "G", who is heterozygous for R297Q, seems perfectly healthy. Login to comment 34 ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln We are establishing a breeding programme to obtain lambs that are homozygous for the R297Q variant. Login to comment 35 ABCC7 p.Arg297Gln We are establishing a breeding programme to obtain lambs that are homozygous for the R297Q variant. Login to comment 57 ABCC7 p.Arg297Gln 9 Graham C, Goon P, Hill A, Cutting G, Curristan S, Nevin N. Identification of a new mutation (R297Q) in exon 7 of the CFTR gene in a Northern Ireland family. Login to comment 60 ABCC7 p.Arg297Gln Identification of a new mutation (R297Q) in exon 7 of the CFTR gene in a Northern Ireland family. Login to comment 61 ABCC7 p.Arg297Gln 11 Dorval I, Jezequel P, Chauvel B, et al. French CF family genotype analysis shows that the R297Q mutation is a rare polymorphism. Login to comment 63 ABCC7 p.Arg297Gln 12 Dorval I, Jezequel P, Roussey M, et al. A French CF family genetic analysis shows that the R297Q associated with the T7 allele in the intron 8 polypyrimidine track is not involved in the CF disease. Login to comment 65 ABCC7 p.Arg297Gln 11 Dorval I, Jezequel P, Chauvel B, et al. French CF family genotype analysis shows that the R297Q mutation is a rare polymorphism. Login to comment 67 ABCC7 p.Arg297Gln 12 Dorval I, Jezequel P, Roussey M, et al. A French CF family genetic analysis shows that the R297Q associated with the T7 allele in the intron 8 polypyrimidine track is not involved in the CF disease. Login to comment