ABCMdb

ABCC7 p.Met82Val

CF databases:	c.244A>G , p.Met82Val (CFTR1) ? , The mutation was detected by DGGE analysis and characterized by direct sequencing. We have seen it only once, in over 400 control chromosomes from Italian population.
Predicted by SNAP2:	A: N (66%), C: N (53%), D: D (85%), E: D (80%), F: N (53%), G: D (75%), H: D (80%), I: N (82%), K: D (85%), L: N (82%), N: D (80%), P: D (75%), Q: D (75%), R: D (85%), S: D (53%), T: N (57%), V: N (82%), W: D (80%), Y: D (53%),
Predicted by PROVEAN:	A: N, C: N, D: D, E: D, F: N, G: D, H: D, I: N, K: N, L: N, N: D, P: D, Q: N, R: D, S: N, T: N, V: N, W: N, Y: N,

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[hide] Gender-sensitive association of CFTR gene mutation... Mol Hum Reprod. 2005 Aug;11(8):607-14. Epub 2005 Aug 26. Morea A, Cameran M, Rebuffi AG, Marzenta D, Marangon O, Picci L, Zacchello F, Scarpa M
Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility.
Mol Hum Reprod. 2005 Aug;11(8):607-14. Epub 2005 Aug 26., [PMID:16126774]

Abstract [show]
Human infertility in relation to mutations affecting the cystic fibrosis transmembrane regulator (CFTR) gene has been investigated by different authors. The role of additional variants, such as the possible forms of the thymidine allele (5T, 7T and 9T) of the acceptor splice site of intron 8, has in some instances been considered. However, a large-scale analysis of the CFTR gene and number of thymidine residues, alone and in combination, in the two sexes had not yet been addressed. This was the aim of this study. Two groups were compared, a control group of 20,532 subjects being screened for perspective reproduction, and the patient group represented by 1854 idiopathically infertile cases. Analyses involved PCR-based CFTR mutations assessment, reverse dot-blot IVS8-T polymorphism analyses, denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. The expected 5T increase in infertile men was predominantly owing to the 5/9 genotypic class. The intrinsic rate of 5T fluctuated only slightly among groups, but some gender-related differences arose when comparing their association. Infertile men showed a significantly enriched 5T + CFTR mutation co-presence, distributed in the 5/9 and 5/7 classes. In contrast, females, from both the control and the infertile groups, showed a trend towards a pronounced reduction of such association. The statistical significance of the difference between expected and observed double occurrence of 5T + CFTR traits in women suggests, in line with other reports in the literature, a possible survival-hampering effect. Moreover, regardless of the 5T status, CFTR mutations appear not to be involved in female infertility. These results underline the importance of (i) assessing large sample populations and (ii) considering separately the two genders, whose genotypically opposite correlations with these phenomena may otherwise tend to mask each other.

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76 This test involved nine subjects from the infertile group, revealing the occurrence of the following rare mutations: E217G, T1054A, W356X, D443Y and 3667insTC in males and L997F and R297Q in females and 29 subjects from the control, in which we found: A1009T, D110Y, E826K, G1069R, G1130A, G194V, I556V, L320F, M348K, M82V, P1290T, R117C, R352W, R74W, S42F, S660T, S911R, S912L, T1086A, T582S, V920L and Y89C. Login to comment

[hide] Deletion of CFTR translation start site reveals fu... Cell Physiol Biochem. 2009;24(5-6):335-46. Epub 2009 Nov 4. Ramalho AS, Lewandowska MA, Farinha CM, Mendes F, Goncalves J, Barreto C, Harris A, Amaral MD
Deletion of CFTR translation start site reveals functional isoforms of the protein in CF patients.
Cell Physiol Biochem. 2009;24(5-6):335-46. Epub 2009 Nov 4., [PMID:19910674]

Abstract [show]
BACKGROUND/AIMS: Mutations in the CFTR gene cause Cystic Fibrosis (CF) the most common life-threatening autosomal recessive disease affecting Caucasians. We identified a CFTR mutation (c.120del23) abolishing the normal translation initiation codon, which occurs in two Portuguese CF patients. This study aims at functionally characterizing the effect of this novel mutation. METHODS: RNA and protein techniques were applied to both native tissues from CF patients and recombinant cells expressing CFTR constructs to determine whether c.120del23 allows CFTR protein production through usage of alternative internal codons, and to characterize the putative truncated CFTR form(s). RESULTS: Our data show that two shorter forms of CFTR protein are produced when the initiation translation codon is deleted indicating usage of internal initiation codons. The N-truncated CFTR generated by this mutation has decreased stability, very low processing efficiency, and drastically reduced function. Analysis of mutants of four methionine codons downstream to M1 (M82, M150, M152, M156) revealed that each of the codons M150/M152/M156 (exon 4) can mediate CFTR alternative translation. CONCLUSIONS: The CFTR N-terminus has an important role in avoiding CFTR turnover and in rendering effective its plasma membrane traffic. These data correlate well with the severe clinical phenotype of CF patients bearing the c.120del23 mutation.

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126 jointly mutated into valines and the respective stable cells wereanalysedbyimmunoblotforCFTR.ResultsinFig.5A reveal the presence of two proteins (D and E) for single mutants of M82V, M150V, M152V and M156V (lanes 36, respectively) and also for the double mutants M150V/ M152, M150V/M156V and M152V/M156V (lanes 7-9). Login to comment
130 Individual and double mutations of M82V, M150V and M152V (lanes 5-8) did not cause loss of either protein species D or E, consistent with the corresponding constructs in the in vivo assay. Login to comment
131 The mutant M82V/M150V/M152V (lane 4) does not alter the production of proteins D and E either. Login to comment
133 Thus, this species likely corresponds to the CFTR variant resulting from usage of M150/M152 or M156 (and not of M82 because the M82V mutation alone did not abolish the appearance of this band). Login to comment
140 Lanes 3-10 correspond to the proteins produced by the methionines mutants all in the c.120del23-CFTR pNUT background: lane 3, M82V; lane 4, M150V; lane 5 M152V; lane 6, M156V; lane 7, M150V/M152V; lane 8, M150V/M156V; lane 9, M152V/M156V; lane 10, M150V/M152V/M156V. Login to comment
144 Lanes 2-8 all in pSP73: 2, CFTR exons 2-24; 3, M82V/ M150V/M152V/M156V; 4, M82V/M150V/M152V; 5, M82/M152V; 6, M82V/M150V;7, M150; 8, M82V. Login to comment

[hide] Genomic landscape of non-small cell lung cancer in... Cell. 2012 Sep 14;150(6):1121-34. doi: 10.1016/j.cell.2012.08.024. Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RK
Genomic landscape of non-small cell lung cancer in smokers and never-smokers.
Cell. 2012 Sep 14;150(6):1121-34. doi: 10.1016/j.cell.2012.08.024., [PMID:22980976]

Abstract [show]
We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs.

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76 We identified five point mutations involving the CFTR gene in four samples; these included four missense (LUC18: M82V, LUC9: R170L, F354I, and A309S from panel screening) and one nonsense (LUC18: S478*) mutations. Login to comment
77 Two of the five point mutations involving CFTR (M82V and S478*) have been previously reported in patients with cystic fibrosis (Koukourakis et al., 2003). Login to comment