ABCC7 p.Asn1088Asp
| ClinVar: |
c.3262A>G
,
p.Asn1088Asp
?
, not provided
|
| CF databases: |
c.3262A>G
,
p.Asn1088Asp
(CFTR1)
?
, This mutation was found in one CF patient with [delta]F508 on the other chromosome and probably associated with R75Q. The patient had sweat chloride of 69 meq/l, pancreatic sufficiency and mild lung disease.
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| Predicted by SNAP2: | A: N (72%), C: N (82%), D: D (75%), E: D (66%), F: D (59%), G: D (66%), H: D (71%), I: N (61%), K: D (63%), L: N (57%), M: N (66%), P: D (59%), Q: N (78%), R: D (59%), S: N (72%), T: N (82%), V: N (72%), W: D (71%), Y: D (75%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[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.Asn1088Asp 11788090:27:414
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.Asn1088Asp 11788090:75:600
status: NEWX
ABCC7 p.Asn1088Asp 11788090:75:630
status: NEW116 N1088D.
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ABCC7 p.Asn1088Asp 11788090:116:0
status: NEW119 The N1088D was found in two siblings (genotype N1088D/DF508) with PS, and mild or no lung disease.
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ABCC7 p.Asn1088Asp 11788090:119:4
status: NEWX
ABCC7 p.Asn1088Asp 11788090:119:47
status: NEW120 There was a third CFTR variant, R75Q, found in these patients and associated with the N1088D allele.
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ABCC7 p.Asn1088Asp 11788090:120:86
status: NEW172 The remaining missense variants (I506L, N1088D, and R1162Q) can be classified as mild alleles because they are associated with a milder CF phenotypein genotypes with a severe second allele.
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ABCC7 p.Asn1088Asp 11788090:172:40
status: NEW[hide] Predictors of deterioration of lung function in cy... Pediatr Pulmonol. 2002 Jun;33(6):483-91. Schaedel C, de Monestrol I, Hjelte L, Johannesson M, Kornfalt R, Lindblad A, Strandvik B, Wahlgren L, Holmberg L
Predictors of deterioration of lung function in cystic fibrosis.
Pediatr Pulmonol. 2002 Jun;33(6):483-91., [PMID:12001283]
Abstract [show]
The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.The severity of pulmonary disease was to some extent predicted by CFTR genotype. Furthermore, the present investigation is the first long-term study showing a significantly more rapid deterioration of lung function in patients with concomitant diabetes mellitus. Besides diabetes mellitus, pancreatic insufficiency and chronic Pseudomonas colonization were found to be negative predictors of pulmonary function. In contrast to several other reports, we found no significant differences in lung function between genders. Patients with pancreatic sufficiency have no or only a slight decline of lung function with age once treatment is started, but an early diagnosis in this group is desirable.
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121 TABLE 3CFTR Mutations Associated With Pancreatic Sufficiency in Swedish CF Population Y109C S549I/S549I Y109N S945L R117C N1088D À R75Q R117H G1244E L206W 711 þ 3A !G T338I 1249 À 5A !G A455E 2789 þ 5G !
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ABCC7 p.Asn1088Asp 12001283:121:122
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.Asn1088Asp 17400678:30:225
status: NEW[hide] Atypical cystic fibrosis and CFTR-related diseases... Clin Rev Allergy Immunol. 2008 Dec;35(3):116-23. Paranjape SM, Zeitlin PL
Atypical cystic fibrosis and CFTR-related diseases.
Clin Rev Allergy Immunol. 2008 Dec;35(3):116-23., [PMID:18493878]
Abstract [show]
Cystic fibrosis (CF), which is among the most common life-shortening recessive illnesses, is caused by mutations of the CF transmembrane conductance regulator (CFTR) and typically involves chronic infection and progressive obstruction of the respiratory tract as well as pancreatic exocrine insufficiency. Disease severity, to some extent, correlates with organ sensitivity to CFTR dysfunction and to the amount of functional protein, which is influenced by the type of mutation. Atypical CF represents approximately 2% of affected individuals, and includes cases presenting in adolescence or adulthood with pancreatic exocrine sufficiency, normal or borderline sweat chloride concentrations, or with a single predominant clinical feature. This review briefly describes diagnostic methods and phenotypic characteristics of classic and atypical CF, as well as CFTR-related diseases, conditions in which mutated CFTR may contribute to the pathogenesis but do not strictly fit established diagnostic criteria.
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64 Determination of the transepithelial nasal potential difference has been beneficial in establishing a CF Table 1 Mutations, sites, and molecular consequences associated with either an atypical presentation of CF respiratory disease or pancreatic sufficiency or late-onset pancreatic insufficiency (http:// www.genet.sickkids.on.ca) Mutation Site Consequence Atypical presentation M1210I Exon 19 Met to Ile at 1210 S1455X Exon 24 Ser to Stop at 1455 1811+18G→A Intron 11 mRNA splicing defect L346P Exon 7 Leu to Pro at 346 Y161D Exon 4 Tyr to Asp at 161 R31C Exon 2 Arg to Cys at 31 I752S Exon 13 Ile to Ser at 752 2811G/T Exon 15 Sequence variation Pancreatic sufficiency or late-onset pancreatic insufficiency R600G Exon 13 Arg to Gly at 600 D1152H Exon 18 Asp to His at 1152 Y89C Exon 3 Tyr to Cys at 89 R117H Exon 4 Arg to His at 117 D110E Exon 4 Asp to Glu at 110 296 + 3insT Intron 2 mRNA splicing defect E217G Exon 6a Glu to Gly at 217 V392G Exon 8 Val to Gly at 392 N1088D Exon 17b Asn to Asp at 1088 S737F Exon 13 Missense 1716+1G→A Intron 10 mRNA splicing defect R334W Exon 7 Arg to Trp at 334 R347P Exon 7 Arg to Pro at 347 A455E Exon 9 Ala to Glu at 455 P574H Exon 12 Pro to His at 574 3850-3T→G Intron 19 mRNA splicing defect diagnosis in many atypical cases.
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ABCC7 p.Asn1088Asp 18493878:64:980
status: NEWX
ABCC7 p.Asn1088Asp 18493878:64:996
status: NEW[hide] Multidrug resistance in the chronic lymphoprolifer... Leuk Lymphoma. 2010 Oct;51(10):1793-804. Drain S, Catherwood MA, Alexander HD
Multidrug resistance in the chronic lymphoproliferative disorders.
Leuk Lymphoma. 2010 Oct;51(10):1793-804., [PMID:20615085]
Abstract [show]
Multidrug resistance (MDR) is a phenomenon in malignancy whereby tumor cells generate mechanisms to resist cytotoxic treatments. Several such mechanisms have been identified. However, to date the most significant research on MDR has involved the adenosine triphosphate binding cassette (ABC) transporter proteins, including P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP). These proteins have natural functions involving substrate transport in normal cells but are detrimental to treatment when expressed in the membrane of tumor cells. It remains unclear whether ABC mediated MDR functions primarily through protein up-regulation or via a relevant signaling mechanism, or is simply due to selective pressure on an already resistant tumor cell subpopulation. Here we present an overview of MDR in the chronic lymphoproliferative disorders (CLPDs), in particular that attributed to the ABC transporter protein family.
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188 Exon rs designation Allele change Synonymous/ non-synonymous Residue effect 3 rs28381804 C-T Non-synonymous Leu-17-Phe 3 rs41304191 T-C Synonymous Leu-19-Leu 3 rs9332385 A-G Synonymous Leu-19-Leu 3 rs9282564 G-A Non-synonymous Leu-21-Asn 5 rs1202183 G-A Non-synonymous Ser-44-Asn 5 rs41315618 C-A Non-synonymous Leu-60-Ile 5 rs9282565 A-C Non-synonymous Glu-80-Ala 5 rs35810889 C-T Non-synonymous Thr-89-Met 7 rs61607171 C-T Non-synonymous Thr-144-Ile 7 rs61122623 A-G Non-synonymous Ile-168-Val 8 rs1128500 T-C Synonymous Ser-180-Ser 8 rs60419673 G-A Non-synonymous Ser-183-Asn 8 rs1128501 T-G Non-synonymous Val-185-Gly 8 rs1128502 T-A Synonymous Gly-185-Gly 9 rs2235022 G-A Synonymous Glu-243-Glu 9 rs28381867 A-G Synonymous Ala-246-Ala 9 rs36008564 G-A Non-synonymous Val-261-Ile 12 rs2229109 A-G Non-synonymous Asn-400-Ser 13 rs1128503 C-T{ Synonymous Gly-412-Gly 13 rs35068177 G-A Synonymous Thr-436-Thr 13 rs41311775 A-G Synonymous Arg-442-Arg 15 rs35633772 T-C Synonymous Ile-539-Ile 15 rs60247941 G-T Synonymous Ala-544-Ala 15 rs2235012 C-G Synonymous Leu-554-Leu 15 rs56871767 A-G Synonymous Thr-558-Thr 15 rs59697741 T-C Synonymous Ser-565-Ser 15 rs28381902 A-G Non-synonymous Lys-566-Glu 16 rs28381914 T-C Non-synonymous Cys-593-Arg 16 rs56107566 A-G Non-synonymous His-593-Arg 16 rs28381915 T-C Synonymous Ile-598-Ile 16 rs2235036 A-G Non-synonymous Thr-599-Ala 16 rs57001392 T-G Non-synonymous Tyr-613-Asp 17 rs35657960 G-T Non-synonymous Arg-662-Leu 17 rs35023033 T-C Non-synonymous Cys-669-Arg 17 rs59340265 T-C Synonymous Asp-679-Asp 18 rs41316450 A-T Non-synonymous Lys-736-Ile 21 rs41305517 A-G Non-synonymous Asn-800-Asp 21 rs2235039 A-G Non-synonymous Met-801-Val 22 rs2032581 G-A Non-synonymous Val-829-Ile 22 rs28381966 G-A Synonymous Val-835-Val 22 rs28381967 G-A Non-synonymous Val-836-Ile 22 rs36105130 G-A Non-synonymous Met-849-Ile 22 rs9282563 T-C Synonymous Leu-884-Leu 22 rs2032582 G-T/A{ Non-synonymous Thr-893-Ala/Ser 25 rs56849127 A-G Non-synonymous Asn-992-Ser 25 rs72552784 A-G Non-synonymous Thr-999-Ala 25 rs2235044 A-G Synonymous Pro-1028-Pro 26 rs28401798 G-C Non-synonymous Ala-1051-Pro 26 rs2707944 C-G Non-synonymous Ala-1063-Gly 26 rs2707943 G-C Synonymous Gly-1063-Gly 26 rs57521326 A-G Non-synonymous Asn-1088-Asp 27 rs41309225 G-A Non-synonymous Glu-1099-Lys 27 rs55852620 C-A Non-synonymous Pro-1107-Gln 27 rs35730308 C-T Non-synonymous Arg-1108-Trp 27 rs34748655 T-C Synonymous Ala-1132-Ala 27 rs41309228 T-G Non-synonymous Ile-1137-Ser 27 rs2229107 A-T Non-synonymous Thr-1141-Ser 27 rs1045642 C-T{ Synonymous Ile-1145-Ile 28 rs59241388 G-A Non-synonymous Glu-1168-Lys 29 rs41309231 T-A Non-synonymous Asp-1223-Glu (continued) P-gp [78].
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ABCC7 p.Asn1088Asp 20615085:188:2247
status: NEW