ABCC7 p.Val603Phe
| ClinVar: |
c.1807G>T
,
p.Val603Phe
?
, not provided
|
| CF databases: |
c.1807G>T
,
p.Val603Phe
(CFTR1)
D
, This mutation was found together with a sequence polymorphism at nucleotide position 1929 where A was present instead of T. V603F was found in 2 CF patients of East Indian origin. One of them carried [delta]F508 on the other allele, with sweat chloride level of 102 meq/l, pancreatic insufficiency and moderate lung disease. The other patient was found to carry the 5T variant in intron 8 but the phase with V603F (ie. cis or trans) could not be determined; the sweat chloride level of this patient was low 33 meq/l; pancreatic sufficient; mild lung disease.
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| Predicted by SNAP2: | A: D (75%), C: D (66%), D: D (95%), E: D (91%), F: D (91%), G: D (91%), H: D (91%), I: N (66%), K: D (95%), L: D (85%), M: D (85%), N: D (91%), P: D (95%), Q: D (91%), R: D (95%), S: D (91%), T: D (85%), W: D (95%), Y: D (91%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Expression of cystic fibrosis transmembrane conduc... Hepatology. 2000 Aug;32(2):334-40. Kinnman N, Lindblad A, Housset C, Buentke E, Scheynius A, Strandvik B, Hultcrantz R
Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosis.
Hepatology. 2000 Aug;32(2):334-40., [PMID:10915740]
Abstract [show]
The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated liver disease, and non-CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epithelial cells in patients carrying the DeltaF508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of DeltaF508 CFTR processing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease.
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No. Sentence Comment
49 Clinical and Laboratory Data in Patients With CF at the Time of Liver Biopsy Patient No Genotype Gender/ Age (yr) Body Weight (kg) Height (cm) FEV1.0 (% pred) Serum ALT (kat/L) GGT (kat/L) Blood Prothrombin time (%) 1 ⌬F508/⌬F508 F/10 38 137 85 0.55 0.20 89 2 ⌬F508/⌬F508 M/10 33 146 99 0.44 0.22 55 3 ⌬F508/⌬F508 M/13 48 168 91 0.54 0.41 64 4 ⌬F508/⌬F508 M/18 69 180 82 0.78 0.59 37 5 ⌬F508/1112delT M/4 16 101 ND 0.85 0.73 38 6 ⌬F508/E640 F/8 29 138 84 0.52 0.39 92 7 ⌬F508/V603F F/8 22 122 100 0.56 0.17 115 8 ⌬F508/394delTT F/10 23 127 90 0.44 0.20 112 9 ⌬F508/3659delC M/38 60 165 103 0.49 1.10 86 10 1112delT/1112delT M/5 22 108 ND 0.63 0.11 122 11 R764X/R764X M/22 68 188 72 0.56 0.26 67 NOTE. Reference range: ALT, F Ͻ .60, M Ͻ .80; GGT, F Ͻ .8, M Ͻ 1.3; Blood-prothrombin time, 70-130.
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ABCC7 p.Val603Phe 10915740:49:569
status: NEW52 Ultrasonographic and Light Microscopic Findings of the Liver in Patients With CF Patient No Genotype Ultrasonography Light Microscopy Echogenecity Microgallbladder Fatty Infiltration Inflammatory Cells Bile-Duct Proliferation Fibrosis 1 ⌬F508/⌬F508 - No ϩ - ϩ ϩϩ 2 ⌬F508/⌬F508 ϩϩ No ϩ - - - 3 ⌬F508/⌬F508 ϩ No ϩ - - ϩ 4 ⌬F508/⌬F508 ϩϩ ND ϩϩ ϩϩ ϩ ϩ 5 ⌬F508/1112delT - No - ϩϩ ϩϩ ϩϩϩ 6 ⌬F508/E640 ϩ No - ϩ - - 7 ⌬F508/V603F - No ϩϩ - ϩ ϩ 8 ⌬F508/394delTT - No - - - ϩ 9 ⌬F508/3659delC ϩϩ No ϩϩ - - ϩ 10 1112delT/1112delT - Yes - - - ϩ 11 R764X/R764X ϩϩ Yes ϩϩ - - ϩ NOTE.
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ABCC7 p.Val603Phe 10915740:52:655
status: NEW92 Results of Immunohistochemical Staining in Liver Sections from CF Patients Patient No Genotype CFTR CK 19 ICAM-1 ␣-SMA CD 3 CD68 1 ⌬F508/⌬F508 ϩϩ ϩϩ ϩ ϩϩ ϩ N 2 ⌬F508/⌬F508 ϩϩ ϩ - - N N 3 ⌬F508/⌬F508 ϩϩ ϩ - - N N 4 ⌬F508/⌬F508 ϩϩ ϩϩ - ϩ ϩϩ ϩ 5 ⌬F508/1112delT ϩ ϩϩϩ ϩ ϩϩ ϩϩ ϩ 6 ⌬F508/E640 ϩ ϩ - - ϩ N 7 ⌬F508/V603F ϩ ϩϩ ϩ ϩ N N 8 ⌬F508/394delTT ϩ ϩ - - N N 9 ⌬F508/3659delC ϩ ϩ - ϩϩ N N 10 1112delT/1112delT - ϩ - ϩϩ N N 11 R764X/R764X - ϩ - ϩϩ N N NOTE. CFTR: - negative staining, ϩ weak positive staining of bile-duct cells, ϩϩ positive staining of bile-duct cells.
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ABCC7 p.Val603Phe 10915740:92:601
status: NEW[hide] Spectrum of mutations in the CFTR gene of patients... Genet Test. 2001 Fall;5(3):235-42. Strandvik B, Bjorck E, Fallstrom M, Gronowitz E, Thountzouris J, Lindblad A, Markiewicz D, Wahlstrom J, Tsui LC, Zielenski J
Spectrum of mutations in the CFTR gene of patients with classical and atypical forms of cystic fibrosis from southwestern Sweden: identification of 12 novel mutations.
Genet Test. 2001 Fall;5(3):235-42., [PMID:11788090]
Abstract [show]
Cystic fibrosis (CF) is caused by mutations in the CFTR gene. The spectrum of CFTR mutations varies between populations and depends on different factors, such as ethnic background and geographical location. The extensive CFTR mutation screening of 129 patients with classical or atypical CF from the south-western region of Sweden revealed the presence of 37 CFTR mutations, including 12 novel alleles. The overall mutation detection rate in this study population was 92%, the highest among all tested regions in Sweden. Eight mutations with a frequency above 1% (DeltaF508, 394delTT, R117C, 3659delC, E60X, 1112delT, R764X, and 621 + 1G --> T) accounted for 78% of CF chromosomes and have been recommended for inclusion in the CFTR mutation screening panel for molecular diagnosis of CF in this region. The multiple occurrence of specific CFTR alleles less common than the predominant DeltaF508 mutation (394delTT, R117C, 3659delC) allowed for genotype-phenotype comparisons and revealed consistent relationships between these mutations and disease severity.
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No. Sentence Comment
27 MUTATIONS IDENTIFIED IN 258 CHROMOSOMES IN THE CF POPULATION ATTENDING THE SOUTH-WESTERN SWEDISH CF CENTRE Location in the Frequency of Mutation gene, exon Number of mutations mutation (%) Homozygotes Heterozygotes DF508 10 161 62.4 56 49 394delTT 3 13 5.0 3 7 R117C 4 7 2.7 7 3659delC 19 5 1.9 5 E60X 3 4 1.6 4 1112delT 7 4 1.6 1 2 R764X 13 4 1.6 1 2 621 1 1G ® T 4 3 1.2 3 G551D 11 2 0.8 2 I506L 10 2 0.8 2 N1088D (R75Q) 17b 2 0.8 2 Q1238X 19 2 0.8 2 R117H (IVS8-5T) 4 2 0.8 2 V603F (IVS8-5T) 13 2 0.8 2 1716G ® A 10 2 0.8 2 R75Q 3 2 0.8 2 R533X 11 1 0.4 1 2329A ® G Promoter 1 0.4 1 297-3 C ® A 2 1 0.4 1 Y161D 4 1 0.4 1 994del9 Exon/intron 6b 1 0.4 1 1154insTC 7 1 0.4 1 W361R 7 1 0.4 1 T338I 7 1 0.4 1 1249-5A ® G Intron 7 1 0.4 1 1717-2A ® G Intron 10 1 0.4 1 R560T 11 1 0.4 1 E1401X 23 1 0.4 1 3126del4 17a 1 0.4 1 S945L 15 1 0.4 1 R668C 13 1 0.4 1 2622 1 2del6 Intron 13 1 0.4 1 R1162Q Exon 19 1 0.4 1 3849 1 10kbC ® T Intron 19 1 0.4 1 R74W Exon 3 1 0.4 1 2363C ® T Promoter 1 0.4 1 IVS8-5Ta Intron 8 1 0.4 1 Unidentified 20 7.8 Total 258 100 61 116 The new mutations are displayed in bold.
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ABCC7 p.Val603Phe 11788090:27:484
status: NEW75 CLINICAL DATA FOR THE CF PATIENTS CARRYING NEW MUTATIONS Age PI Lung Sweat (years) at or disease Cl Mutations diagnosis PSb (severity) (mmol/liter) Additional symptoms Frameshift 1112delT/1112delT 4 PI 111 110 1112delT/DF508 0.3 PI 111 112 1112delT/DF508 0.2a PI 111 110 3126del4/E60X 2 PI 11 130 994del9/DF508 0.08 PI 2 120 Meconium ileus RNA splice 297-3C ® A/DF508 0.3 PI 1 120 2622 1 2del6/DF508 0.25 PI 111 100 Nonsense E1401X/unknown 6 PS 2 52 Poor growth, fat malabsorption, abnormal electrophysiological response in the intestinal mucosal biopsy Missense V603F, IVS8-5T/DF508 2 PI 1 101 N1088D, R75Q/DF508 4a PS 2 78 N1088D, R75Q/DF508 2 PS 2 75 Y161D/DF508 0.4 PI 1 83 Malabsorption I506L/DF508 42.5 PS 111 103 I506L/3659delC 30 PS 111 80 R1162Q/unknown nvc PS 1 6 Frequent pneumonias V603F, IVS8-5T/unknown nvc PS (1) 24 Sinusitis, severe recurrent hypoglycemia, nasal polyps, abdominal pain Promoter?
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ABCC7 p.Val603Phe 11788090:75:568
status: NEWX
ABCC7 p.Val603Phe 11788090:75:799
status: NEW99 V603F.
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ABCC7 p.Val603Phe 11788090:99:0
status: NEW100 This missense mutation in exon 13 (R-domain) was caused by a transversion of G to T at the position 1939 of the CFTR gene and, in consequence,the change of valine to phenylalanine at amino acid position 603.
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ABCC7 p.Val603Phe 11788090:100:156
status: NEW101 This allele was found in a female patient with the DF508 as the second allele, and the RNA splice site IVS8-5T variantco-segregatingwith the V603F mutation.
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ABCC7 p.Val603Phe 11788090:101:141
status: NEW171 Two of them (V603F and Y161D) are associated with PI, moderate-to-severe lung disease, and elevated sweat chloride levels.
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ABCC7 p.Val603Phe 11788090:171:13
status: NEW[hide] Association between serum oncofetal antigens CA 19... Acta Paediatr. 2003 Nov;92(11):1267-71. Gronowitz E, Pitkanen S, Kjellmer I, Heikinheimo M, Strandvik B
Association between serum oncofetal antigens CA 19-9 and CA 125 and clinical status in patients with cystic fibrosis.
Acta Paediatr. 2003 Nov;92(11):1267-71., [PMID:14696845]
Abstract [show]
In cystic fibrosis (CF), mucus plugging in the airways and in the gastrointestinal tract leads to severe morbidity and mortality. The mucin-associated antigens CA 19-9 and CA 125 are markers of gastrointestinal malignancy, and CA 19-9 has also been reported in association with pulmonary function in CF. AIM: To test whether these antigens might serve as markers for the severity of pulmonary and gastrointestinal disease in CF. METHODS: In 99 patients, aged 1 to 48 y, serum levels of CA 19-9 and CA 125 were measured by RIA and ELISA and related to clinical data. RESULTS: Patients with severe mutations had significantly increased serum levels of CA 125, indicating an association with a more severe CF phenotype. This was further supported by the association with lung function, chronic pulmonary colonization of Pseudomonas aeruginosa and pancreatic insufficiency. CA 19-9 was also shown to be associated with lung function and Ps. aeruginosa colonization. No gastrointestinal malignancy was found in our patients despite very high values of CA 19-9 in some patients. During a 5-y follow-up, the very high serum levels of CA 19-9 decreased along with improved general condition of the patients. CONCLUSION: Increased serum levels of CA 125 in CF patients were associated with severe cystic fibrosis transmembrane conductance regulator mutations and a severe phenotype. Both antigens were associated with pseudomonas colonization and lung function and CA 125 also with pancreatic insufficiency. The estimates of CA 19-9 are hampered by the influence of the Lewis histo-blood group system on the synthesis of CA 19-9.
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45 The remaining 23 patients had at least one mild (I506L, R117C, S945L, T338I, W301R, 3849 10KBC → T, 1249-5 → G, R117H, R75Q), moderate (G551D, R560T, V603F) or unknown mutation.
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ABCC7 p.Val603Phe 14696845:45:171
status: NEW[hide] Airway nitric oxide in patients with cystic fibros... Chest. 2007 Jun;131(6):1857-64. Epub 2007 Mar 30. Keen C, Olin AC, Edentoft A, Gronowitz E, Strandvik B
Airway nitric oxide in patients with cystic fibrosis is associated with pancreatic function, Pseudomonas infection, and polyunsaturated fatty acids.
Chest. 2007 Jun;131(6):1857-64. Epub 2007 Mar 30., [PMID:17400678]
Abstract [show]
BACKGROUND: Airway nitric oxide (NO) is low or normal in cystic fibrosis (CF) patients. This may affect bacterial status since NO has antimicrobial properties. Arachidonic acid (AA), which is increased in the serum and airways of CF patients, has been shown to reduce NO levels. The aim of this study was to investigate whether airway NO level correlates with genotype and pancreatic function, and whether low airway NO level is associated with bacterial infection and increased serum AA level in CF patients. METHOD: Nasal NO (nNO) and exhaled NO (eNO) were measured according to the European Respiratory Society/American Thoracic Society standard in 59 CF patients aged 7 to 55 years, 80% of whom were pancreatic insufficient (PI) and 51% were chronically infected with Pseudomonas aeruginosa. RESULTS: PI CF patients had significantly lower nNO levels than pancreatic-sufficient (PS) patients. Airway NO level did not correlate with lung function or inflammatory parameters. PI patients chronically infected with P aeruginosa had significantly lower nNO levels than noninfected PI patients. nNO level correlated inversely with the AA/docosahexaenoic acid ratio, and eNO with the essential fatty acid (FA) deficiency index, which is the ratio between mead acid and AA. CONCLUSIONS: CF patients with PI, which is associated with more severe genotypes, had lower airway NO levels than patients with PS. Low NO level was correlated to chronic P aeruginosa infection, and an association was found between airway NO level and the abnormal serum phospholipid FA pattern.
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No. Sentence Comment
30 Patients in group 3 were heterozygous for mutations dF508 and V603F, R560T, or 621 ϩ 1G-T; group 4 patients were heterozygous for mutations dF508, 3659del C, or 394delTT and a mutation linked to a "mild" phenotype (eg, N1088D, R117C, R117H, R75Q, R658X, S945L, 1154insTC, or T338I).
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ABCC7 p.Val603Phe 17400678:30:62
status: NEW