ABCC7 p.Gly1237Ser
| CF databases: |
c.3709G>A
,
p.Gly1237Ser
(CFTR1)
?
, This mutation was found by SSCA and direct DNA sequencing in a woman 35 years old with bronchiectasis.
|
| Predicted by SNAP2: | A: N (61%), C: N (53%), D: D (59%), E: N (53%), F: D (80%), H: N (72%), I: D (59%), K: N (82%), L: D (53%), M: N (66%), N: N (82%), P: D (53%), Q: N (82%), R: N (82%), S: N (72%), T: N (66%), V: N (53%), W: D (85%), Y: D (63%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: D, R: N, S: N, T: D, V: D, W: D, Y: D, |
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[hide] Bronchiectasis in adult patients: an expression of... Clin Genet. 2004 Jun;65(6):490-5. Casals T, De-Gracia J, Gallego M, Dorca J, Rodriguez-Sanchon B, Ramos MD, Gimenez J, Cistero-Bahima A, Olveira C, Estivill X
Bronchiectasis in adult patients: an expression of heterozygosity for CFTR gene mutations?
Clin Genet. 2004 Jun;65(6):490-5., [PMID:15151509]
Abstract [show]
While all patients with cystic fibrosis (CF) have mutations in both CFTR alleles, often only one CFTR change is detected in patients with other lung disorders. The aim of this study was to investigate whether heterozygosity for CFTR mutations could be a determinant risk factor in the development of bronchiectasis in adult patients. We have performed the CFTR gene analysis in a cohort of 55 bronchiectasis adult patients with unknown etiology. The 5T variant (TG)m and the M470V polymorphisms were also analyzed. A general population in which the same molecular analysis was previously performed was used as the control group. The mutational spectrum of patients was also compared with that found in our CF population. CFTR mutations/variants were found in 20 patients (36%), 14 with only one mutant gene (25%). All six patients colonized by Staphylococcus aureus presented with at least one CFTR change (p = 0.001). No statistical significance was observed between patients with and without mutations for other clinical features. The 5T variant was found in four patients. Additionally, 90% of patients with mutations had the more functional M470 allele (p < 0.001). These results suggest the involvement of the CFTR gene in bronchiectasis of unknown etiology in adult patients.
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No. Sentence Comment
61 Among the 11 missense mutations, the (G1237S) a G > A substitution at nucleotide 3841 is reported for the first time and was detected in two sibs, the brother presenting with oligozoospermia.
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ABCC7 p.Gly1237Ser 15151509:61:38
status: NEW[hide] Genetic, cell biological, and clinical interrogati... Genet Med. 2014 Aug;16(8):625-32. doi: 10.1038/gim.2014.4. Epub 2014 Feb 20. Molinski SV, Gonska T, Huan LJ, Baskin B, Janahi IA, Ray PN, Bear CE
Genetic, cell biological, and clinical interrogation of the CFTR mutation c.3700 A>G (p.Ile1234Val) informs strategies for future medical intervention.
Genet Med. 2014 Aug;16(8):625-32. doi: 10.1038/gim.2014.4. Epub 2014 Feb 20., [PMID:24556927]
Abstract [show]
PURPOSE: The purpose of this study was to determine the molecular consequences of the variant c.3700 A>G in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, a variant that has been predicted to cause a missense mutation in the CFTR protein (p.Ile1234Val). METHODS: Clinical assays of CFTR function were performed, and genomic DNA from patients homozygous for c.3700 A>G and their family members was sequenced. Total RNA was extracted from epithelial cells of the patients, transcribed into complementary DNA, and sequenced. CFTR complementary DNA clones containing the missense mutation p.Ile1234Val or a truncated exon 19 (p.Ile1234_Arg1239del) were constructed and heterologously expressed to test CFTR protein synthesis and processing. RESULTS: In vivo functional measurements revealed that the individuals homozygous for the variant c.3700 A>G exhibited defective CFTR function. We show that this mutation in exon 19 activates a cryptic donor splice site 18 bp upstream of the original donor splice site, resulting in deletion of six amino acids (r.3700_3717del; p.Ile1234_Arg1239del). This deletion, similar to p.Phe508del, causes a primary defect in folding and processing. Importantly, Lumacaftor (VX-809), currently in clinical trial for cystic fibrosis patients with the major cystic fibrosis-causing mutation, p.Phe508del, partially ameliorated the processing defect caused by p.Ile1234_Arg1239del. CONCLUSION: These studies highlight the need to verify molecular and clinical consequences of CFTR variants to define possible therapeutic strategies.
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131 Interestingly, the CF Mutation Database5 contains several disease-associated mutations within the p.Ile1234_Arg1239 sequence and includes c.3705T>G (p.Ser1235Arg), c.3709G>A (p.Gly1237Ser), c.3713A>G (p.Gln1238Arg), c.3712C>T (p.Gln1238X), and c.3717G>C (p.Arg1239Ser).
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ABCC7 p.Gly1237Ser 24556927:131:177
status: NEW132 These mutations were each found in one or two individuals of European descent (i.e., Belgian, Spanish, French, and English), and the clinical presentation varied from a mild phenotype, in which the mutation was detected at 40 years of age (p.Gly1237Ser), with pancreatic sufficiency and forced expiratory volume in 1 s >70%, to a more severe CF phenotype (p.Gln1238X, in trans with p.Phe508del) that was diagnosed at birth and manifested with pancreatic insufficiency.
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ABCC7 p.Gly1237Ser 24556927:132:242
status: NEW