ABCMdb

ABCC7 p.Gly1244Arg

ClinVar:	c.3731G>A , p.Gly1244Glu D , Pathogenic c.3730G>A , p.Gly1244Arg ? , not provided c.3731G>T , p.Gly1244Val ? , not provided
CF databases:	c.3731G>A , p.Gly1244Glu D , CF-causing ; CFTR1: This missense mutation was detected in an Italian PI patient through DGGE screening and direct sequencing. The nucleotide changeis G3863-A and generates a Gly to Glu substitution in codon 1244. As a result the recognition site for MboII starting at nucleotide 3863 is destroyed. The mutation was found only once out of 110 non-[delta]F508 Italian CF chromosomes analyzed in Paris by the DGGE technique and it was not found in 45 non-[delta]F508 CF French chromosomes. c.3730G>A , p.Gly1244Arg (CFTR1) ? , This mutation was identified on one Italian CF chromosome, applying a protocol of extended mutational search (5?-flanking region, all the exons and adjacent intronic regions) by direct sequencing. No other mutations were found on the same allele. The mutation 3849+10KbCtoT was found on the other allele. The G1244R mutation was not found in 232 alleles from the general population. c.3731G>T , p.Gly1244Val (CFTR1) ? , This mutation in exon 20 reults in the substitution of valine for glycine at amino acid position 1244 (G1244V). The mutation was detected by SSCP analysis of exon 20 followed by direct sequencing. The nucleotide substitution abolishes an MboII restriction site. G1244V was detected in a single CF allele out of 105 non-[delta]F508 CF chromosomes screened. It has not been found on any of the 50 normal alleles screened. The mutation was found in the maternal CF allele in a patient of Bulgarian ehtnic background. The chromosomal haplotype is 2/1/1/16/31/13 (XV-2c/KM.19/d9/IVS8-CA/IVS17b-TA/IVS17b-CA). The paternal CF chromosome carries the G542X mutation.
Predicted by SNAP2:	A: D (95%), C: D (95%), D: D (95%), E: D (66%), F: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (95%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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[hide] A 96-well formatted method for exon and exon/intro... Anal Biochem. 2006 Jun 15;353(2):226-35. Epub 2006 Apr 5. Lucarelli M, Narzi L, Piergentili R, Ferraguti G, Grandoni F, Quattrucci S, Strom R
A 96-well formatted method for exon and exon/intron boundary full sequencing of the CFTR gene.
Anal Biochem. 2006 Jun 15;353(2):226-35. Epub 2006 Apr 5., [PMID:16635477]

Abstract [show]
Full genotypic characterization of subjects affected by cystic fibrosis (CF) is essential for the definition of the genotype-phenotype correlation as well as for the enhancement of the diagnostic and prognostic value of the genetic investigation. High-sensitivity diagnostic methods, capable of full scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, are needed to enhance the significance of these genetic assays. A method for extensive sequencing of the CFTR gene was optimized. This method was applied to subjects clinically positive for CF and to controls from the general population of central Italy as well as to a single subject heterozygous for a mild mutation and with an uncertain diagnosis. Some points that are crucial for the optimization of the method emerged: a 96-well format, primer project and purification, and amplicon purification. The optimized method displayed a high degree of diagnostic sensitivity; we identified a subset of 13 CFTR mutations that greatly enhanced the diagnostic sensitivity of common methods of mutational analysis. A novel G1244R disease causing mutation, leading to a CF phenotype with pancreatic sufficiency but early onset of pulmonary involvement, was detected in the subject with an uncertain diagnosis. Some discrepancies between our results and previously published CFTR sequence were found.

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5 A novel G1244R disease causing mutation, leading to a CF phenotype with pancreatic sufficiency but early onset of pulmonary involvement, was detected in the subject with an uncertain diagnosis. Some discrepancies between our results and previously published CFTR sequence were found. Login to comment
31 To verify the absence of the novel G1244R mutation in the general population, the exon 20 of a further 90 subjects from the general population was analyzed. Login to comment
99 DHPLC assay design With the aim of optimizing a rapid method for the search of the novel G1244R mutation on a large number of samples, a DHPLC assay was designed and performed by a WAVE DNA Fragment Analysis System on a DNASep column (Transgenomic). Login to comment
122 Novel G1244R mutation and biochemical and clinical characterization of a subject with uncertain diagnosis The application of this protocol to the subject with an uncertain diagnosis allowed us to detect the novel CFTR mutation G1244R (3862 G->A, glycine to arginine) in exon 20 (Fig. 2A) [1] in the critical NBF2 domain. Login to comment
123 The analysis of allelic segregation in the parents assigned the 3849+10kbC->T (carried by the mother) and G1244R (carried by the father) mutations to different alleles. Login to comment
125 The novel G1244R mutation was not found in the other 73 unknown CF alleles analyzed, nor was it found in the 232 alleles from the general population. Login to comment
127 The biochemical and clinical characteristics of the 3849+10KbC->T/G1244R genotype are as follows. Login to comment
153 Several findings suggest that the novel G1244R should be classified as a disease-causing mutation. Login to comment
156 The G1244R mutation was absent from the 232 alleles in the general population and in the other affected subjects studied, and it was found as the only mutation on one allele of 1 other subject studied, with no other mutation on this allele being detectable by extended sequencing. Login to comment
159 The G1244R mutation by sequencing (A) and by DHPLC (B). Login to comment
162 Nevertheless, additional functional studies should be performed to assess the exact clinical severity of the G1244R mutation. Login to comment
163 The fact that this subject escaped neonatal screening demonstrates that both the G1244R and 3849+10kbC->T mutations yield a negative neonatal IRT dosage; with regard to the latter mutation, this finding is in contrast to some previous reports [39]. Login to comment
165 The frequency of the G1244R mutation must be calculated on a larger number of CF subjects to ascertain whether it is a rare mutation; however, the frequency of the G1244E mutation, one of the other mutations in the same codon, was found to be approximately 0.3%, which is relatively high. Login to comment

[hide] CFTR mutations spectrum and the efficiency of mole... PLoS One. 2014 Feb 26;9(2):e89094. doi: 10.1371/journal.pone.0089094. eCollection 2014. Zietkiewicz E, Rutkiewicz E, Pogorzelski A, Klimek B, Voelkel K, Witt M
CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.
PLoS One. 2014 Feb 26;9(2):e89094. doi: 10.1371/journal.pone.0089094. eCollection 2014., [PMID:24586523]

Abstract [show]
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR). In light of the strong allelic heterogeneity and regional specificity of the mutation spectrum, the strategy of molecular diagnostics and counseling in CF requires genetic tests to reflect the frequency profile characteristic for a given population. The goal of the study was to provide an updated comprehensive estimation of the distribution of CFTR mutations in Polish CF patients and to assess the effectiveness of INNOLiPA_CFTR tests in Polish population. The analyzed cohort consisted of 738 patients with the clinically confirmed CF diagnosis, prescreened for molecular defects using INNOLiPA_CFTR panels from Innogenetics. A combined efficiency of INNOLiPA CFTR_19 and CFTR_17_TnUpdate tests was 75.5%; both mutations were detected in 68.2%, and one mutation in 14.8% of the affected individuals. The group composed of all the patients with only one or with no mutation detected (109 and 126 individuals, respectively) was analyzed further using a mutation screening approach, i.e. SSCP/HD (single strand conformational polymorphism/heteroduplex) analysis of PCR products followed by sequencing of the coding sequence. As a result, 53 more mutations were found in 97 patients. The overall efficiency of the CF allele detection was 82.5% (7.0% increase compared to INNOLiPA tests alone). The distribution of the most frequent mutations in Poland was assessed. Most of the mutations repetitively found in Polish patients had been previously described in other European populations. The most frequent mutated allele, F508del, represented 54.5% of Polish CF chromosomes. Another eight mutations had frequencies over 1%, 24 had frequencies between 1 and 0.1%; c.2052-2053insA and c.3468+2_3468+3insT were the most frequent non-INNOLiPA mutations. Mutation distribution described herein is also relevant to the Polish diaspora. Our study also demonstrates that the reported efficiency of mutation detection strongly depends on the diagnostic experience of referring health centers.

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71 Exon / intron (legacy) Exon / intron (Ensembl) Protein change SVM value cDNA (HGVS nomenclature) gDNA (cDNA +132 bp) Number of PL CF chromosomes Reference a Mutations in trans Pathogenic mutations 1 1 L15Ffs10X c.43delC 175delC 1 CFMDB 1717-1G.A 2 2 G27V 21.92 c.80G.T 212G.T 1 Novel F508del 2 2 S18RfsX16 c.54-5940_273 +10250del21kb exon2,3del21kb 66 IL19 various CF mutations i2 i2 IVS2_Donor c.164+1G.A 296+1G.A 3 CFMDB various CF mutations 3 3 G85E 22.61 c.254G.A 386G.A 1 IL17 unknown 3 3 E60X c.178G.T 310G.T 0 IL17 x 3 3 L88IfsX22 c.262_263delTT 394delTT 0 IL17 x 4 4 E92K 21.92 c.274G.A 406G.A 2 CFMDB c.164+1G.A; c.2051- 2AA.G 4 4 L101X c.302T.G 434T.G 1 CFMDB c.3717+12191C.T 4 4 K114IfsX5 c.341_353del13bp 473del13bp 1 Novel F508del 4 4 R117H 20.35 c.350G.A 482G.A 5 IL17 F508del; 2x unknown 4 4 R117C 22.07 c.349C.T 481C.T 2 CFMDB S1206X;1x unknown 4 4 L137_L138insT c.412_413insACT L138ins 1 CFMDB F508del 4 4 R153I 22.61 c.458G.T 590G.T 2 Novel F508del; c.3527delC i4 i4 IVS4_Donor c.489+1G.T 621+1G.T 5 IL17 F508del; c.489+1G.T 5 5 L165X c.494T.A 626T.A 1 Novel F508del i5 i5 IVS5_Donor c.579+1G.T 711+1G.T 0 IL19 x i5 i5 IVS5_Donor c.579+3A.G 711+3A.G 2 CFMDB 2,3del21kb; c.2052-3insA i5 i5 IVS5_Donor c.579+5G.A 711+5G.A 0 IL17 x 7 8 F311L 20.90 c.933C.G 965C.G 2 CFMDB 2x F508 7 8 G314R 20.58 c.940G.A 1072G.A 4 CFMDB various CF mutations 7 8 F316LfsX12 c.948delT 1078delT 1 IL17 unkown 7 8 R334W 22.41 c.1000C.T 1132C.T 6 IL17 various CF mutations 7 8 I336K 22.07 c.1007T.A 1139T.A 2 CFMDB 2,3de21kb; F508del 7 8 R347P 22.27 c.1040G.C 1172G.C 11 IL17 various CF mutations i7 i8 IVS8_Donor c.1116+2T.A 1248+2T.A 1 Novel Q1412X 9 10 A455E 22.61 c.1364C.A 1496C.A 0 IL17 x i9 i10 IVS10_Donor c.1392+1G.A 1524+1G.A 1 CFMDB c.3816-7delGT 10 11 S466X c.1397C.G 1529C.G 1 CFMDB G542X 10 11 I507del c.1519_1521delATC 1651delATC 2 IL19 F508del 10 11 F508del c.1521_1523delCTT 1654delCTT 805 IL19 various CF mutations i10 i11 IVS11_Acceptor c.1585-1G.A 1717-1G.A 27 IL19 various CF mutations 11 12 G542X c.1624G.T 1756G.T 25 IL19 various CF mutations 11 12 G551D 21.24 c.1624G.T 1756G.T 5 IL19 various CF mutations 11 12 Q552X c.1654C.T 1786C.T 0 IL19 x 11 12 R553X c.1657C.T 1789C.T 14 IL19 various CF mutations 11 12 R560T 21.92 c.1679G.C 1811G.C 0 IL19 x i12 i13 IVS13_Donor c.1766+1G.A 1898+1G.A 6 IL19 various CF mutations i12 i13 IVS13_Donor c.1766+1G.C 1898+1G.C 1 CFMDB F508del 13 14 H620P 21.73 c.1859A.C 1991A.C 1 CFMDB F508del 13 14 R668C//G576A 21.61//1.73 c.2002C.T//c.1727G.C 2134C.T// 1859G.C 5 b CFMDB// rs1800098 c.1585-1G.A; 4 unknown 13 14 L671X c.2012delT 2143delT 27 IL17 various CF mutations 13 14 K684SfsX38 c.2051_2052delAAinsG 2183AA.G 10 IL17 various CF mutations 13 14 K684NfsX38 c.2052delA 2184delA 0 IL17 x 13 14 Q685TfsX4 c.2052_2053insA 2184insA 15 CFMDB various CF mutationsc , 1 unknown Table 2. Cont. Exon / intron (legacy) Exon / intron (Ensembl) Protein change SVM value cDNA (HGVS nomenclature) gDNA (cDNA +132 bp) Number of PL CF chromosomes Reference a Mutations in trans 13 14 L732X c.2195T.G 2327T.G 1 CFMDB F508del 14A 15 R851X c.2551C.T 2683C.T 3 CFMDB various CF mutations 14A 15 I864SfsX28 c.2589_2599del11bp 2721del11bp 2 CFMDB F508del; 2,3del21kb i14B i16 IVS16_Donor c.2657+2_2657+3insA 2789+2insA 1 CFMDB F508del i14B i16 IVS16_Donor c.2657+5G.A 2789+5G.A 0 IL17 unkown 15 17 Y919C 21.02 c.2756A.G 2888A.G 1 CFMDB unknown 15 17 H939HfsX27 c.2817_2820delTACTC 2949delTACTC 1 Novel unkown i15 i17 IVS17_Donor c.2908+3A.C 3040+3A.C 1 Novel F508del i16 i18 IVS18_Donor c.2988+1G.A 3120+1G.A 0 IL19 x 17A 19 I1023_V1024del c.3067_3072delATAGTG 3199del6 0 IL19 x i17A i19 IVS19 c.3140-26A.G 3272-26A.G 9 IL19 various CF mutations 17B 20 L1065R 21.90 c.3194T.G 3326T.G 1 CFMDB F508del 17B 20 Y1092X c.3276C.A 3408C.A 1 CFMDB R334W i18 i21 IVS21_Donor c.3468+2_3468+3insT 3600+2insT 11 CFMDB various CF mutationsd , 1 unknown 18 21 E1126EfsX7 c.3376_3379delGAAG 3508delGAAG 1 Novel F508del 19 22 R1158X c.3472C.T 3604C.T 2 CFMDB F508del; R553X 19 22 R1162X c.3484C.T 3616C.T 1 IL17 F508del 19 22 L1177SfsX15 c.3528delC 3659delC 4 IL17 various CF mutations 19 22 S1206X c.3617C.A 3749C.A 1 CFMDB R117C i19 i22 IVS22 c.3717+12191C.T 3849+10kbC.T 58 IL17 various CF mutations 20 23 G1244R 22.62 c.3730G.C 3862G.C 1 CFMDB F508del 20 23 S1251N 22.28 c.3752G.A 3884G.A 0 IL19 x 20 23 L1258FfsX7 c.3773_3774insT 3905insT 0 IL19 x 20 23 V1272VfsX28 c.3816_3817delGT 3944delGT 1 CFMDB c.1392+1G.A 20 23 W1282X c.3846G.A 3978G.A 9 IL19 various CF mutations 21 24 N1303K 22.62 c.3909C.G 4041C.G 18 IL19 various CF mutations 22 25 V1327X c.3979delG 4111delG 1 Novel F508del 22 25 S1347PfsX13 c.4035_4038dupCCTA c.4167dupCCTA 1 CFMDB 2,3del21kb 23 26 Q1382X c.4144C.T 4276C.T 1 CFMDB F508del 23 26 Q1412X c.4234C.T 4366C.T 2 CFMDB F508del; c.1116+2T.A i23 i26 IVS26_Donor c.4242+1G.T 4374+1G.T 1 CFMDB F508del Sequence changes of uncertain pathogenic effect, tentatively counted as mutations 6A 6 E217G 0.30 c.650A.G 782A.G 1 CFMDB; rs1219109046 unknown 7 8 R352Q 20.01 c.1055G.A 1187G.A 1 CFMDB; rs121908753 F508del 7 8 Q359R 0.33 c.1076A.G 1208A.G 1 CFMDB F508del i8 i9 IVS9 c.1210-12T5_1210- 34_35 (TG)12 1332-12Tn_- 34TGm 6 CFMDB F508del; 3x unknown i8 i9 IVS9 c.1210-12T5_1210- 34_35 (TG)13 1332-12Tn_- 34TGm 2 CFMDB 2143delT; 1x unknown i8 i9 IVS9 c.1210-12T8 1332-12Tn 1 Novel unknown 10 11 I506V 20.21 c.1516A.G 1648A.G 1 CFMDB; rs1800091 unknown 12 13 V562L 0.79 c.1684G.C 1816G.C 1 CFMDB; rs1800097 unknown 13 14 G723V 0.44 c.2168G.T 2300G.T 1 CFMDB; rs200531709 unknown 15 17 D924N 0.03 c.2770G.A 2902G.A 1 CFMDB; rs201759207 unknown patient with F508del on another allele) was not supported by the SVM value (+0.35); the patient was PS and had ambiguous chloride values (45, 64 and 83 mmol/L). 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[hide] A Genotypic-Oriented View of CFTR Genetics Highlig... Mol Med. 2015 Apr 21;21:257-75. doi: 10.2119/molmed.2014.00229. Lucarelli M, Bruno SM, Pierandrei S, Ferraguti G, Stamato A, Narzi F, Amato A, Cimino G, Bertasi S, Quattrucci S, Strom R
A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis.
Mol Med. 2015 Apr 21;21:257-75. doi: 10.2119/molmed.2014.00229., [PMID:25910067]

Abstract [show]
Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype-phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype-phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype-phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway.

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181 Old nomenclature (legacy name) New nomenclature (HGVS name) Nucleotidic Aminoacidic Nucleotidic Aminoacidic Position notation notation Position notation notation Exon 10 1567G>T E479X exon 11 c.1435G>T p.Glu479* Exon 9 1456A>T K442X exon 10 c.1324A>T p.Lys442* Exon 11 1717G>A D529N exon 12 c.1585G>A p.Asp529Asn Exon 10 1526C>A T465N exon 11 c.1394C>A p.Thr465Asn Exon 2 188G>A W19X(TAG) exon 2 c.56G>A p.Trp19*(TAG) Exon 22 4256A>C H1375P exon 25 c.4124A>C p.His1375Pro Exon 13 2467C>T Q779X exon14 c.2335C>T p.Gln779* Exon 20 3871G>C G1247R(G>C) exon 23 c.3739G>C p.Gly1247Arg Exon 20 3862G>A G1244R exon 23 c.3730G>A p.Gly1244Arg Intron 7 1249-8A>G - intron 8 c.1117-8A>G - Exon 3 299A>G E56G exon 3 c.167A>G p.Glu56Gly Table 2. Login to comment
200 [Trp1282*];[Gly1247Arg] 12e 3849+10kbC>T/G1244R c. Login to comment
228 The G1244R (p.Gly1244Arg) mutation was already published by us (24) when the patient was 7 years old; here we provide a further 7-year follow-up report following that description. Login to comment
229 The G1244R (p.Gly1244Arg) mutation was found in a CF-PS male patient, diagnosed at 14 months of age on the basis of symptoms, with a 3849+10kbC>T/G1244R 2 6 4 | L U C A R E L L I E T A L . Login to comment
390 L1077P c.3230T>C CF-PI CF-causing p.Leu1077Pro Y1092X(C>A) c.3276C>A CF-PI CF-causing p.Tyr1092* M1137V c.3409A>G CFTR-RD nd p.Met1137Val D1152H c.3454G>C CF-PI,CF-PS,CFTR-RD varying clinical consequence p.Asp1152His R1162X c.3484C>T CF-PI CF-causing p.Arg1162* D1168G c.3503A>G CFTR-RD nd p.Asp1168Gly 3667ins4 c.3535_3536insTCAA CF-PI CF-causing p.Thr1179IlefsX17 S1206X c.3617C>A uncertain: CF-PI and/or CF-PS nd p.Ser1206* I1234V c.3700A>G CF-PI,CF-PS CF-causing p.Ile1234Val S1235R c.3705T>G CFTR-RD non CF-causing p.Ser1235Arg 3849+10kbC>T c.3717+12191C>T CF-PI,CF-PS CF-causing V1240G c.3719T>G CFTR-RD nd p.Val1240Gly G1244R c.3730G>A uncertain: CF-PI and/or CF-PS nd p.Gly1244Arg G1244E c.3731G>A CF-PI,CF-PS CF-causing p.Gly1244Glu G1247R(G>C) c.3739G>C CF-PS nd p.Gly1247Arg W1282X c.3846G>A CF-PI CF-causing p.Trp1282* Q1291R c.3872A>G CF-PI,CF-PS,CFTR-RD nd p.Gln1291Arg 4016insT c.3884_3885insT CF-PI CF-causing p.Ser1297PhefsX5 4040delA c.3908delA CF-PI nd p.Asn1303ThrfsX25 N1303K c.3909C>G CF-PI CF-causing p.Asn1303Lys ex22-24del c.3964-3890_4443+3143del9454ins5 CF-PI nd ex22,23del c.3964-78_4242+577del1532 CF-PI CF-causing 4168delCTAAGCC c.4036_4042del CF-PI nd p.Leu1346MetfsX6 G1349D c.4046G>A CF-PI CF-causing p.Gly1349Asp H1375P c.4124A>C uncertain: CF-PI and/or CF-PS nd p.His1375Pro S1455X c.4364C>G CF-PS,CFTR-RD nd p.Ser1455* Q1476X c.4426C>T CFTR-RD nd p.Gln1476* nd,Not determined.According to the three rules described (see Materials and Methods),each mutated allele was classified according to its clinical outcome.It was impossible to univocally assign 16 of the 125 different mutated alleles to one or more macrocategories.A comparison with the CFTR2 project (11) (http://www.cftr2.org) is shown.The alleles are ordered according to their nucleotidic position. Login to comment

[hide] Exogenous and endogenous determinants of vitamin K... Sci Rep. 2015 Jul 10;5:12000. doi: 10.1038/srep12000. Krzyzanowska P, Pogorzelski A, Skorupa W, Moczko J, Grebowiec P, Walkowiak J
Exogenous and endogenous determinants of vitamin K status in cystic fibrosis.
Sci Rep. 2015 Jul 10;5:12000. doi: 10.1038/srep12000., [PMID:26160248]

Abstract [show]
Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. The effects of vitamin K supplementation are very ambiguous. Therefore, we aimed to define the determinants of vitamin K deficiency in a large cohort of supplemented - 146 (86.9%) and non-supplemented - 22 (13.1%) CF patients. Vitamin K status was assessed using prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC). The pathological PIVKA-II concentration (>/= 2 ng/ml) and abnormal percentage of osteocalcin (>/= 20%) were found in 72 (42.8%) and 60 (35.7%) subjects, respectively. We found that liver involvement, diabetes, and glucocorticoid therapy were potential risk factors for vitamin K deficiency. Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K. However, it seems that there are no good predictive factors of vitamin K deficiency in CF patients in everyday clinical care. Early vitamin K supplementation in CF patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified.

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122 The genotypes of the studied patients were as follows: F508del/F508del (nߙ=Èa;ߙ74); F508del/- (nߙ=Èa;ߙ23); F508del/3849ߙ+Èa;ߙ10ߙkbCߙ>Èa;ߙT (nߙ=Èa;ߙ6); F508del/2143delT (nߙ =Èa;ߙ 6); F508del/R553X (nߙ =Èa;ߙ4); F508del/2183AAߙ>Èa;ߙG (nߙ=Èa;ߙ3); F508del/1717-1G>Èa;A (nߙ=Èa;ߙ3); F508del/CFTRdele2,3(21ߙkb) (nߙ=Èa;ߙ3); F508del/3272-26Aߙ>Èa;ߙG (nߙ=Èa;ߙ 2); F508del/N1303K (nߙ =Èa;ߙ2); F508del/4374ߙ+Èa;ߙ1Gߙ>Èa;ߙT (nߙ=Èa;ߙ1); F508del/621ߙ+Èa;ߙ1Gߙ>Èa;ߙT (nߙ=Èa;ߙ 1); F508del/3659delC (nߙ =Èa;ߙ1); F508del/ G1244R (nߙ =Èa;ߙ 1); F508del/G542X (nߙ =Èa;ߙ 1); F508del/R117H (nߙ =Èa;ߙ 1); F508del/R334W (nߙ =Èa;ߙ1); G542X/- (nߙ=Èa;ߙ2); CFTRdele2,3(21ߙkb)/- (nߙ=Èa;ߙ2); CFTRdele2,3(21ߙkb)/CFTRdele2,3(21ߙkb) (nߙ=Èa;ߙ1); 1717-1-Gߙ>Èa;ߙA/ CFTRdele2,3(21ߙkb) (nߙ=Èa;ߙ1); 3849ߙ+Èa;ߙ10ߙkbCߙ>Èa;ߙT/- (nߙ=Èa;ߙ1); 3849ߙ+Èa;ߙ10ߙkbCߙ>Èa;ߙT/1717ߙ-Èa;ߙ1Aߙ>Èa;ߙG (nߙ=Èa;ߙ1); N1303K/- (nߙ=Èa;ߙ1); N1303K/3272-26Aߙ>Èa;ߙG (nߙ=Èa;ߙ1); G542X/R553X (nߙ=Èa;ߙ1); 1524ߙ+Èa;ߙ1Gߙ>Èa;ߙA/E585X (nߙ=Èa;ߙ1); 2183AAߙ>Èa;ߙG/- (nߙ=Èa;ߙ1); 2184insA/622-1Gߙ>Èa;ߙA (nߙ=Èa;ߙ1); 2143delT/R1102X (nߙ=Èa;ߙ1); 3272-26Aߙ>Èa;ߙG/- (nߙ=Èa;ߙ1); 3659delC/- (nߙ=Èa;ߙ1); R347P/R347P (nߙ=Èa;ߙ1); S1196X/Q1382X (nߙ=Èa;ߙ1). Login to comment