ABCC7 p.Ile105Asn
| ClinVar: |
c.314T>A
,
p.Ile105Asn
?
, not provided
|
| CF databases: |
c.314T>A
,
p.Ile105Asn
(CFTR1)
?
, This possible mutation was found by DGGE and identified by DNA fluorescent sequencing in a CF patient, who is heterozygous for the mutation Q890X. This mutation destroys a restriction site for HinfI.
|
| Predicted by SNAP2: | A: D (91%), C: D (91%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), K: D (95%), L: D (71%), M: D (80%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: N (53%), T: D (95%), V: D (66%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Phenotypic characterisation of patients with inter... Thorax. 2009 Aug;64(8):683-91. Epub 2009 Mar 23. Goubau C, Wilschanski M, Skalicka V, Lebecque P, Southern KW, Sermet I, Munck A, Derichs N, Middleton PG, Hjelte L, Padoan R, Vasar M, De Boeck K
Phenotypic characterisation of patients with intermediate sweat chloride values: towards validation of the European diagnostic algorithm for cystic fibrosis.
Thorax. 2009 Aug;64(8):683-91. Epub 2009 Mar 23., [PMID:19318346]
Abstract [show]
BACKGROUND: In patients with symptoms suggestive of cystic fibrosis (CF) and intermediate sweat chloride values (30-60 mmol/l), extensive CFTR gene mutation analysis and nasal potential difference (NPD) measurement are used as additional diagnostic tests and a positive result in either test provides evidence of CFTR dysfunction. To define the phenotype of such patients and confirm the validity of grouping them, patients with intermediate sweat chloride values in whom either additional CF diagnostic test was abnormal were compared with subjects in whom this was not the case and patients with classic CF. METHODS: The phenotypic features of four groups were compared: 59 patients with CFTR dysfunction, 46 with an intermediate sweat chloride concentration but no evidence of CFTR dysfunction (CF unlikely), 103 patients with CF and pancreatic sufficiency (CF-PS) and 62 with CF and pancreatic insufficiency (CF-PI). RESULTS: The CFTR dysfunction group had more lower respiratory tract infections (p = 0.01), more isolation of CF pathogens (p<0.001) and clubbing (p = 0.001) than the CF unlikely group, but less frequent respiratory tract infections with CF pathogens than the CF-PS group (p = 0.05). Patients in the CF-PS group had a milder phenotype than those with PI. Many features showed stepwise changes through the patient groups. CONCLUSION: Patients with intermediate sweat chloride values and two CFTR mutations or an abnormal NPD measurement have a CF-like phenotype compatible with CFTR dysfunction and, as a group, differ phenotypically from patients with intermediate sweat chloride values in whom further CF diagnostic tests are normal as well as from CF-PS and CF-PI patients.
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60 Table 2 CFTR mutations in the patient subgroups CF-PS CFTR dysfunction CF unlikely Genotype Subjects (n) Genotype Subjects (n) Genotype Subjects (n) F508del*/Not found 12 F508del*/3849+10 kb(C.T){ 11 Not found/Not found 39 Not found/Not found 10 F508del*/R117H{ 7 F508del*/Not found 4 F508del*/3849+10 kb(C.T){ 7 F508del*/Not found 7 IVS8-5T{/Not found 1 F508del*/R347P{ 5 Not found/Not found 5 S1235E/E528E 1 F508del*/R117H{ 4 F508del*/D1152H{ 4 No mutation analysis 1 F508del*/2789+5G.A{ 4 F508del*/IVS8-5T{ 4 Total 46 F508del*/S945L* 3 F508del*/S945L* 2 2789+5G.A{/Not found 3 W1282X*/IVS8-5T{ 2 F508del*/3272-26 A.G{ 2 F508del*/R1070W{ 1 F508del*/A455E{ 2 F508del*/L159S 1 F508del*/711+5G.A 2 F508del*/T1246I 1 F508del*/2789+5G.A 2 F508del*/L165S 1 G542X*/R334W{ 2 W1282X*/D1152H{ 1 F508del*/R334W{ 2 R1162X*/D1152H{ 1 R347P{/Not found 2 R347Hu/D1152H{ 1 F508del*/2116delCTAA 1 R553X*/R117H{ 1 F508del*/IVS8-5T{ 1 3659delC*/R117H{ 1 F508del*/D1152H{ 1 3849+10kb(C.T){/G551R 1 F508del*/711+3A.G 1 R1162X*/3849+10 kb(C.T){ 1 F508del*/L206W{ 1 2789+5G.A{/Not found 1 F508del*/I336K{ 1 G542X*/T854A 1 F508del*/G970D 1 R553X*/Q1463H 1 F508del*/L159S 1 S1235R/R668C 1 F508del*/R751L 1 2789+5G.A{/S977F 1 F508del*/E656X 1 No mutation analysis 1 F508del*/4015delA 1 Total 59 F508del*/Y913S 1 F508del*/L165S 1 F508del*/2143delT 1 G551D*/I336K{ 1 G551D*/3272-26A.G{ 1 G551D*/711+3A.G 1 R553X*/4005+2T.C 1 R553X*/E92K{ 1 G542X*/L206W{ 1 W1282X*/I336K 1 R1162X*/3849+10 kb(C.T){ 1 R1162X*/2789+5G.A{ 1 574delA*/3141del9 1 9890X/I105N 1 R334W{/R1070Q{ 1 3272-26A.G{/4218insT 1 3272-26A.G{/L165S 1 711+3A.G/G1244E 1 R352Q/1812-1G.A 1 F1052V/IVS8-5T{ 1 R74W/D1270N 1 1898-3G.A/1898-3G.A 1 1717-1G.A*/R334W{ 1 3659delC*/Not found 1 394delTT/Not found 1 R1162X*/Not found 1 R553X*/Not found 1 R117H{/Not found 1 G85E*/Not found 1 3849+10k(C.T){/Not found 1 Total 103 *Mutation class I, II or III.
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ABCC7 p.Ile105Asn 19318346:60:1520
status: NEW[hide] Identification of the second CFTR mutation in pati... Asian J Androl. 2010 Nov;12(6):819-26. Epub 2010 Jul 26. Giuliani R, Antonucci I, Torrente I, Grammatico P, Palka G, Stuppia L
Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols.
Asian J Androl. 2010 Nov;12(6):819-26. Epub 2010 Jul 26., [PMID:20657600]
Abstract [show]
Congenital bilateral absence of vas deferens (CBAVD) is a manifestation of the mildest form of cystic fibrosis (CF) and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator (CFTR) gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach: (i) first, a reverse dot-blot analysis was performed to detect mutations with regional impact; (ii) next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and (iii) finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.
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No. Sentence Comment
77 Patient 15 exhibited a T-to-A change in exon 4, nucleotide 446, which leads to the substitution of an isoleucine with an asparagine in position 105 of the CFTR protein (I105N) .
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ABCC7 p.Ile105Asn 20657600:77:169
status: NEW81 Patient First-level CFTR screening CFTR Italian MLPA analysis DHPLC analysis Final genotype (36 mutations + 5T allele) regional kit 1 [delta]F508/5T - - - [delta]F508/5T 2 [delta]F508/5T - - - [delta]F508 /5T 3 [delta]F508/5T - - - [delta]F508/5T 4 [delta]F508/5T - - - [delta]F508/5T 5 [delta]F508 /5T - - - [delta]F508/5T 6 G542X/5T - - - [delta]F508/5T 7 G542X/5T - - - [delta]F508/5T 8 W1282X/5T - - - W1282X/5T 9 [delta]F508/wt [delta]F508/T338I - - [delta]F508/T338I 10 [delta]F508/wt [delta]F508/wt [delta]F508/wt [delta]F508/wt [delta]F508/wt 11 5T/wt 5T/T338I - - 5T/T338I 12 5T/wt 5T/wt 5T/del ex1 - 5T/del ex1 13 5T/wt 5T/wt 5T/del ex19 - 5T/del ex19 14 5T/wt 5T/wt 5T/wt 5T/2811G/T 5T/2811G/T 15 5T/wt 5T/wt 5T/wt 5T/I105N 5T/I105N 16 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt 17 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt 18 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt 19 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt 20 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt 21 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt 22 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt 23 5T/wt 5T/wt 5T/wt 5T/wt 5T/wt Detection rate 8/23 (34.8%) 2/15 (13.3%) 2/13 (15.3%) 2/11 (18.1%) 14/23 (60.8%) Abbreviations: CFTR, cystic fibrosis transmembrane conductance regulator; DHPLC, denaturing high-performance liquid chromatography; MLPA, multiple ligation-dependent probe amplification; wt, wildtype.
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ABCC7 p.Ile105Asn 20657600:81:814
status: NEWX
ABCC7 p.Ile105Asn 20657600:81:824
status: NEW108 In the remaining two patients, DHPLC analysis revealed a 2811G/T and an I105N sequence change.
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ABCC7 p.Ile105Asn 20657600:108:72
status: NEW122 The missense I105N mutation, which was detected in one case by DHPLC, has been previously reported in one patient with full-blown CF in compound heterozygosity with the Q890X mutation (Cystic Fibrosis Mutation Database, Mutation Details) [8].
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ABCC7 p.Ile105Asn 20657600:122:13
status: NEW[hide] [CFTR gene sequencing in a group of Chilean patien... Rev Chil Pediatr. 2014 Jul;85(4):448-54. doi: 10.4067/S0370-41062014000400007. Lay-Son R G, Vasquez D M, Puga Y A, Manque M P, Repetto L G
[CFTR gene sequencing in a group of Chilean patients with cystic fibrosis].
Rev Chil Pediatr. 2014 Jul;85(4):448-54. doi: 10.4067/S0370-41062014000400007., [PMID:25697318]
Abstract [show]
INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations of the CFTR gene, in which over 1,900 different mutations have been identified. In Chile, the diagnosis panel with the 36 most common mutations detects approximately 50% of all alleles, while for Caucasians, it is nearly 90%. The objective of this study is to expand the capacity of mutational screening in Chilean patients and look for recurrent mutations at the national level. METHOD: The detection of unknown pathogenic alleles was assessed by CFTR gene sequencing in a selected group of patients from the National Cystic Fibrosis Foundation (NCFF). 39 patients, who met the CF diagnostic criteria and had only one allele identified according to the mutational panel, were studied. Massive sequencing was performed throughout the investigation and the main CFTR databases were used for analysis. RESULTS: The second pathogenic allele was identified in 16 of 39 patients of this study (41%), finding eleven different mutations that had not been reported in our population. We believe that the reason is that one of the variants had not been previously described. CONCLUSIONS: Mutations that had been described mainly in Hispanic and/or Mediterranean populations were identified. We found a variation that had not been previously reported, but not enough recurrent mutations that could explain the low rate of detection were found. Knowledge about mutations can provide appropriate genetic counseling and will be critical to evaluate the potential use of new targeted therapies for treating them.
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No. Sentence Comment
58 Mutaciones detectadas por secuenciaci&#f3;n masiva en cohorte de 39 pacientes chilenos con FQ portadores de un alelo desconocido Mutaci&#f3;n detectada (nomenclatura actual*) n de alelos Reporte en pacientes con FQ (no de alelos) Efecto Denominaci&#f3;n antigua c.1330_1331delAT 3 Argentina (1)a Prote&#ed;na truncada por generaci&#f3;n de cod&#f3;n de t&#e9;rmino 1460delAT c.314T>A 2 Francia (1)a Cambio de amino&#e1;cido Isoleucina por Asparagina I105N c.4046G>A 2 Italia (7)b,c , EEUU (1)d Cambio de amino&#e1;cido Glicina por Aspartato G1349D c.148T>C 2 Espa&#f1;a (2)e Cambio de amino&#e1;cido Serina por Prolina S50P c.695T>A 1 Espa&#f1;a (14)e,f , EEUU (hispanos) (5)g,h Francia (2)a , Brasil (1)i Cambio de amino&#e1;cido Valina por Aspartato V232D c.3266G>A 1 Espa&#f1;a (5)e , Brasil (2)i,j , EEUU (hispanos) (2)g , Argentina (1)k , Israel (1)l Prote&#ed;na truncada por generaci&#f3;n de cod&#f3;n de t&#e9;rmino W1089X c.1647T>G 1 Emiratos &#c1;rabes Unidos (> 30)m,n , Colombia (4)o , Israel (4)p , Argelia (2)p , Marruecos (2)q , Reino Unido (2)p , Portugal (1)p , Espa&#f1;a (1)p , Francia (1)p , Italia (1)p , Brasil (1)q , Argentina (1)q Cambio de amino&#e1;cido Serina por Arginina S549R(T- >G) c.308G>A 1 No descrita previamente Cambio de amino&#e1;cido Glicina por Glutamato G103E c.1680-1G>A 1 Espa&#f1;a (1)r Alteraci&#f3;n en splicing 1812-1G->A c.1679+1G>C 1 Francia (2)s Macedonia (1)s , Alteraci&#f3;n en splicing 1811+1G->C c.490-2A>G 1 Argentina (1)t Alteraci&#f3;n en splicing 622-2A->G FQ: Fibrosis qu&#ed;stica.
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ABCC7 p.Ile105Asn 25697318:58:450
status: NEW[hide] Newborn Screening for Cystic Fibrosis in Californi... Pediatrics. 2015 Dec;136(6):1062-72. doi: 10.1542/peds.2015-0811. Epub 2015 Nov 16. Kharrazi M, Yang J, Bishop T, Lessing S, Young S, Graham S, Pearl M, Chow H, Ho T, Currier R, Gaffney L, Feuchtbaum L
Newborn Screening for Cystic Fibrosis in California.
Pediatrics. 2015 Dec;136(6):1062-72. doi: 10.1542/peds.2015-0811. Epub 2015 Nov 16., [PMID:26574590]
Abstract [show]
OBJECTIVES: This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California. METHODS: From July 16, 2007, to June 30, 2012, a total of 2 573 293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values >/=62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with >/=2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling. RESULTS: Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test-positive infants, respectively). CONCLUSIONS: The 3-step model had high detection and low false-positive levels in this diverse population.
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No. Sentence Comment
108 [1210-12[5]];[1210-34TG[11]] (IVS8 (TG)11-5T)f 1 2 c.531delT (663delT) / c.314T.A (I105N)e 1 3 c.1521_1523delCTT (F508del) / c.1841A.G (D614G)e 1 3 c.1521_1523delCTT (F508del) / c.290T.C (V97A)e 1 3 c.1519_1521delATC (I507del) / c.
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ABCC7 p.Ile105Asn 26574590:108:83
status: NEW