ABCC7 p.Lys166Glu
| ClinVar: |
c.496A>G
,
p.Lys166Glu
?
, not provided
|
| CF databases: |
c.496A>G
,
p.Lys166Glu
(CFTR1)
D
, The K166Q mutation was detected in a 16 year old female Korean CF patient. She also inherited the [delta]F508 mutation from her caucasian father. ASO hybridization screening did not detect the K166Q mutation among 47 normal chromosomes of Asian descent. The patient was diagnosed at the age of 10 years with sweat chloride concentration of 111mM. She has mild lung disease and is pancreatic sufficient.
|
| Predicted by SNAP2: | A: D (66%), C: D (59%), D: D (91%), E: D (80%), F: D (85%), G: D (75%), H: D (75%), I: D (80%), L: D (80%), M: D (75%), N: D (63%), P: D (91%), Q: D (59%), R: N (82%), S: D (59%), T: D (59%), V: D (80%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, L: D, M: N, N: N, P: D, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D, |
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[hide] A novel missense mutation A1081P in the cystic fib... J Trop Pediatr. 2004 Aug;50(4):239-40. Ngukam A, Jacquemont ML, Souville I, Viel M, Beldjord C, Hubert D, Hughes JN, Bienvenu T
A novel missense mutation A1081P in the cystic fibrosis transmembrane conductance regulator (CFTR) gene identified in a Laotian patient with congenital bilateral absence of the vas deferens.
J Trop Pediatr. 2004 Aug;50(4):239-40., [PMID:15357566]
Abstract [show]
Cystic fibrosis is the most common autosomal disorder in the Caucasion population. However, the disease is rare in Asia and little is known about the spectrum of CF transmembrane conductance regulator, CFTR, mutations in this population. We studied a 39-year-old Loatian patient with congenital bilateral absence of the vas deferens and identified a novel missense mutation in exon 17b (3373G>C). Identification of novel mutations in this Asian population is of particular interest when designing a genetic testing strategy in Asian countries and also in other countries where immigration from Asia is common.
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No. Sentence Comment
4 Only a few CFTR mutations have been identified in that population (L88X, M152R, K166E, F508del, 1742delAC, 1525-18G>A, 1540del10, L568X, 1898ϩ1G>T, 1898ϩ5G>T, G970D, 451-458del8, 3121-2A>G, H1085R).1-6 We report here a novel missense mutation in a Laotian patient with congenital bilateral absence of the vas deferens (CBAVD).
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ABCC7 p.Lys166Glu 15357566:4:80
status: NEW[hide] Detection of F508del mutation in cystic fibrosis t... Singapore Med J. 2006 Feb;47(2):129-33. Zilfalil BA, Sarina S, Liza-Sharmini AT, Oldfield NJ, Stenhouse SA
Detection of F508del mutation in cystic fibrosis transmembrane conductance regulator gene mutation among Malays.
Singapore Med J. 2006 Feb;47(2):129-33., [PMID:16435054]
Abstract [show]
INTRODUCTION: Cystic fibrosis (CF) is one of the common genetic disorders in the western world. It has been reported to be very rare in Asian populations. According to the Cystic Fibrosis Genetic Analysis Consortium, more than 1,000 mutations of the CF gene have been identified. The CF gene, named the cystic fibrosis transmembrane conductance regulator (CFTR), is located on chromosome 7 and composed of 27 exons. This study aims to detect possible CFTR gene mutations in Malays. METHODS: We analysed 50 blood samples from healthy Malays with no symptoms of CF. DNA was extracted from blood using commercially available extraction kits (Eppendorf, Germany). Identification of CFTR gene mutation was performed using the CF OLA (Oligonucleotide Ligation Assay) kit (Applied Biosystems, USA). The PCR-ligation products were electrophoresed on eight percent sequagel using an ABI PRISM 377 genetic analyser (Applied Biosystems, USA). Electrophoresis data was analysed using the Genotyper software and a report of the CF genotype for all loci tested was created using the CF Genotyper Template software. Out of 50, one sample (two percent) was detected to have the F508del mutation (3bp deletion at exon 10), which is one of the most common CFTR gene mutations in Caucasians. RESULTS: The F508del mutation allele was detected in one subject. This indicates that she was a CF carrier. CONCLUSION: We report the finding of a carrier of the F508del mutation of the CFTR gene in the Malay population. Our finding revealed that CF could also affect the Malay population. Larger studies are necessary to determine the exact gene frequency of this population.
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No. Sentence Comment
76 The novel mutations found in Asian populations include a missense mutation A1081P in CFTR gene reported on a Loatian patient with CBAVD(6) , two novel mutations, E7X and 989-992insA, in a Taiwanese cystic fibrosis patient(7) and three Asian mutations, K166E, L568X and 3121-2A‡G (in homozygosity), reported by Macek et al(8) .
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ABCC7 p.Lys166Glu 16435054:76:252
status: NEW[hide] Sensitivity of the denaturing gradient gel electro... Hum Mutat. 1997;9(2):136-47. Macek M Jr, Mercier B, Mackova A, Miller PW, Hamosh A, Ferec C, Cutting GR
Sensitivity of the denaturing gradient gel electrophoresis technique in detection of known mutations and novel Asian mutations in the CFTR gene.
Hum Mutat. 1997;9(2):136-47., [PMID:9067754]
Abstract [show]
More than 500 mutations have been identified in the CFTR gene, making it an excellent system for testing mutation scanning techniques. To assess the sensitivity of denaturing gradient gel electrophoresis (DGGE), we collected a representative group of 202 CFTR mutations. All mutations analyzed were detected by scanning methods other than the DGGE approach evaluated in this study. DGGE analysis was performed on 24 of the 27 exons and their flanking splice site sequences. After optimization, 201 of the 202 control samples produced an altered migration pattern in the region in which an alteration occurred. The remaining sample was sequenced and found not to have the reported mutation. The ability of DGGE to identify novel mutations was evaluated in three Asian CF patients with four unknown CF alleles. Three novel Asian mutations were detected-K166E, L568X, and 3121-2 A-->G (in homozygosity)-accounting for all CF alleles. These results indicate that an optimized DGGE scanning strategy is highly sensitive and specific and can detect 100% of mutations.
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No. Sentence Comment
8 Three novel Asian mutations were detected-K166E, L568X, and 3121-2 AÃG (in homozygosity)-accounting for all CF alleles.
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ABCC7 p.Lys166Glu 9067754:8:42
status: NEW31 DNA samples from 100 healthy random South Korean individuals were used in population screening for the K166E mutation identified in this study.
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ABCC7 p.Lys166Glu 9067754:31:103
status: NEW58 Population screening for the K166E mutation by ASO hybridization was performed using published conditions, with PCR primers 5i5´ and 5i3´ and mutant probe K166E-MUT; 5´-CTT GAC AGC TCT AAA GTC T-3´, with a final wash at 51°C (Zielenski et al., 1991; Cutting et al., 1992).
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ABCC7 p.Lys166Glu 9067754:58:29
status: NEWX
ABCC7 p.Lys166Glu 9067754:58:165
status: NEW115 Three novel mutations K166E, L568X, and 3121-2 AÃG (in homozygosity) were discovered accounting for all unknown CF alleles (Table 2).
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ABCC7 p.Lys166Glu 9067754:115:22
status: NEW119 The K166E mutation in the Korean-American 17-year-old girl occurs on the CF chromosome inherited from her Asian mother.
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ABCC7 p.Lys166Glu 9067754:119:4
status: NEW123 The K166E mutations may be classified as "mild," with regard to pancreatic function, since this almost adult CF patient remains pancreatic sufficient.
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ABCC7 p.Lys166Glu 9067754:123:4
status: NEW137 Novel CFTR Mutations Identified in Asian CF Patientsa Mutation Nucloetide change Exon/intron Consequence CFTR domain K166E AÃG at 628 E5 Lys à Glu at 166 L568X TÃA at 1835 E12 Leu à stop NBD I 31212 AÃG AÃG at 31212 I16 Splice mutation TM 9 The position of a nucleotide change together with its location in the CFTR gene (E, exon; I, intron) and the amino acid designation are according to Zielenski et al. (1991).
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ABCC7 p.Lys166Glu 9067754:137:117
status: NEW[hide] Human epithelial cystic fibrosis transmembrane con... Biophys J. 1996 Dec;71(6):3148-56. Xie J, Drumm ML, Zhao J, Ma J, Davis PB
Human epithelial cystic fibrosis transmembrane conductance regulator without exon 5 maintains partial chloride channel function in intracellular membranes.
Biophys J. 1996 Dec;71(6):3148-56., [PMID:8968585]
Abstract [show]
The cardiac isoform of the cystic fibrosis transmembrane conductance regulator (CFTR) is a splice variant of the epithelial CFTR, with lacks 30 amino acids encoded by exon 5 in the first intracellular loop. For examination of the role of exon 5 in CFTR channel function, a CFTR deletion mutant, in which exon 5 was removed from the human epithelial CFTR, was constructed. The wild type and delta exon5 CFTR were expressed in a human embryonic kidney cell line (293 HEK). Fully mature glycosylated CFTR (approximately 170 kDa) was immunoprecipitated from cells transfected with wild type CFTR cDNA, whereas cells transfected with delta exon5 CFTR express only a core-glycosylated from (approximately 140 kDa). The Western blot test performed on subcellular membrane fractions showed that delta exon5 CFTR was located in the intracellular membranes. Neither incubation at lower temperature (26 degrees C) nor stimulation of 293 HEK cells with forskolin or CPT-cAMP caused improvement in glycosylation and processing of delta exon5 CFTR proteins, indicating that the human epithelial CFTR lacking exon5 did not process properly in 293 HEK cells. On incorporation of intracellular membrane vesicles containing the delta exon5 CFTR proteins into the lipid bilayer membrane, functional phosphorylation- and ATP-dependent chloride channels were identified. CFTR channels with an 8-pS full-conductance state were observed in 14% of the experiments. The channel had an average open probability (Po) of 0.098 +/- 0.022, significantly less than that of the wild type CFTR (Po = 0.318 +/- 0.028). More frequently, the delta exon5 CFTR formed chloride channels with lower conductance states of approximately 2-3 and approximately 4-6 pS. These subconductance states were also observed with wild type CFTR but to a much lesser extent. Average Po for the 2-3-pS subconductance state, estimated from the area under the curve on an amplitude histogram, was 0.461 +/- 0.194 for delta exon5 CFTR and 0.332 +/- 0.142 for wild type (p = 0.073). The data obtained indicate that deleting 30 amino acids from the first intracellular loop of CFTR affects both processing and function of the CFTR chloride channel.
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No. Sentence Comment
204 The facts that a splice mutation that deletes exon 5 was found to be a cystic fibrosis disease-causing mutant and that there is an array of cystic fibrosis mutations in the region encoded by exon 5 (L165S, K166E, R170C, 1175V, G178R, D192N, D192G, E193K; Fonknechten et al., 1992; Romey et al., 1994; Zielenski et al., 1991; Audrezet et al., 1994; Mercier et al., 1995; Cystic Fibrosis Mutation Data Base) suggest that exon 5 is important for the structure, function, or both of the CFTR chloride channel.
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ABCC7 p.Lys166Glu 8968585:204:206
status: NEW205 The facts that a splice mutation that deletes exon 5 was found to be a cystic fibrosis disease-causing mutant and that there is an array of cystic fibrosis mutations in the region encoded by exon 5 (L165S, K166E, R170C, 1175V, G178R, D192N, D192G, E193K; Fonknechten et al., 1992; Romey et al., 1994; Zielenski et al., 1991; Audrezet et al., 1994; Mercier et al., 1995; Cystic Fibrosis Mutation Data Base) suggest that exon 5 is important for the structure, function, or both of the CFTR chloride channel.
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ABCC7 p.Lys166Glu 8968585:205:206
status: NEW