ABCMdb

PMID: 24586523

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., [PubMed]

Sentences

No. Mutations Sentence Comment

51 ABCC7 p.Arg352Gln ABCC7 p.Asp1152His ABCC7 p.Val562Leu ABCC7 p.Glu217Gly ABCC7 p.Leu967Ser ABCC7 p.Gln359Arg ABCC7 p.Asp924Asn ABCC7 p.Gly723Val Three of them (R352Q, Q359R and D1152H) were in a compound heterozygosity with F508del, six (E217G, I506, V562L, G723V, D924N and L967S) had no accompanying mutation in trans. Login to comment 53 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala Another substitution, G576A (SVM +1.73), was found in three patients, in cis with a deleterious R668C allele (SVM -1.61); the latter was also present without G576A, in two patients (in one with c.1585-1G.A in trans). Login to comment 54 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala In the UMD-CFTR database (www.umd.be/CFTR), G576A and R668C have been reported in cis; in the CFTR2 database both mutations are described as having ''varying consequences``. Login to comment 55 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala Three of our patients carrying R668C were PI, and two appeared PS; PS/PI status was independent on the presence of G576A. Login to comment 56 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala We considered R668C a pathogenic mutation, and G576A - an associated element of a compound allele. Login to comment 57 ABCC7 p.Ser912Leu ABCC7 p.Ser912Leu Finally, S912L (SVM +2.12), found in a single chromosome with F508del in trans, has been reported in the CFMDB as pathogenic only if in cis with c.3067-3072del6; since the latter was not found in the analyzed patient, we considered S912L a neutral polymorphism. Login to comment 59 ABCC7 p.Leu165* ABCC7 p.Val1327* They were present in a single patient each (major manifestation indicated in parentheses), and most were in trans with F508del: L165X (PI; chloride values: 88 and 90 mmol/L); V1327X (meconium ileus, MI; no chloride data available); c.341_353del13bp (PI; chloride values: 131, 143 and 147 mmol/L); c.3376_3379delGAAG (PI; chloride values: 97 and 90); c.2908+3A.C (PS; chloride values: 117, 119 and 182 mmol/ L). Login to comment 60 ABCC7 p.Gln1412* The c.1116+2T.A (no chloride data available) was in trans with Q1412X; for the c.2817_2820delTACTC (PS; normal chloride values: 33 and 52 mmol/L), no second mutation was identified. Login to comment 61 ABCC7 p.Ile752Val ABCC7 p.Arg153Ile ABCC7 p.Gly27Val In case of three novel amino acid substitutions (G27V, R153I and I752V), the possibility that a change represented a nonpathological polymorphism was examined. Login to comment 63 ABCC7 p.Arg153Ile ABCC7 p.Arg153Ile ABCC7 p.Gly27Val ABCC7 p.Gly27Val The SVM values indicated strongly deleterious effect of both R153I and G27V on the protein stability (22.61 and 21.92, respectively), and both positions were conserved in the comparative analysis with orthologues from several Eutherian species (www.ensembl.org); R153I and G27V were therefore assumed to be pathogenic mutations. Login to comment 64 ABCC7 p.Arg153Ile R153I was found in two unrelated patients with pulmonary manifestation and a known CF mutation on another allele (F508del or c.3528delC); the first patient had elevated chloride values (94 and 98 mmol/L), and no chloride data were available for the second patient. Login to comment 65 ABCC7 p.Gly27Val G27V was found in a single patient with PI and pulmonary symptoms (chloride values .100 mmol/L), and was accompanied by F508del on another allele. Login to comment 66 ABCC7 p.Ile752Val The deleterious consequence of I752V (found in a single Table 1. Login to comment 68 ABCC7 p.Ile148Thr Mutations detected in a patient Number of CF patients Alleles with no mutation identified Alleles with CF mutations detected using INNOLiPA tests Further molecular analysis CFTR_19 CFTR_17TnUpdatea both 503 (68.1%) 0 888 (60.2%) 118 (8.0%) Not necessary one 109 (14.8%) 109 98 (6.6%) 11 (0.7%) Yes none 126 (17.1%) 252 0 0 Yes Legend: a I148T included in CFTR-17TnUpdate was not counted as a mutation if not in cis with c.3067-72del6 (l.n. 3199del6); c.1210(-12)Tn site in intron 9 (l.n.IVS8-Tn) without data on the associated TG repeat was not counted as a mutation. Login to comment 71 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ser1251Asn ABCC7 p.Arg352Gln ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Arg1158* ABCC7 p.Gln1412* ABCC7 p.Gln1412* ABCC7 p.Tyr1092* ABCC7 p.Gln552* ABCC7 p.Val562Leu ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Ile506Val ABCC7 p.Arg117Cys ABCC7 p.Arg117Cys ABCC7 p.Glu92Lys ABCC7 p.Glu217Gly ABCC7 p.Ile336Lys ABCC7 p.Glu60* ABCC7 p.Arg851* ABCC7 p.Tyr919Cys ABCC7 p.Phe311Leu ABCC7 p.Ser466* ABCC7 p.Gln359Arg ABCC7 p.His620Pro ABCC7 p.Gly314Arg ABCC7 p.Leu732* ABCC7 p.Asp924Asn ABCC7 p.Ser1206* ABCC7 p.Ser1206* ABCC7 p.Leu1065Arg ABCC7 p.Gln1382* ABCC7 p.Leu671* ABCC7 p.Gly1244Arg ABCC7 p.Gly723Val ABCC7 p.Leu165* ABCC7 p.Val1327* ABCC7 p.Arg153Ile ABCC7 p.Gly27Val 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). Login to comment 73 ABCC7 p.Ile752Val I752V was therefore considered to represent a rare neutral polymorphism rather than a pathogenic mutation. Login to comment 86 ABCC7 p.Arg668Cys ABCC7 p.Gly314Arg The most frequent non-IL alleles identified in this study (i.e. c.2052_2053insA; c.3468+2_3468+3insT; IVS9 T5_TG12-13; R668C; G314R) should be included in the PL population screening panel. Login to comment 101 ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ile148Thr ABCC7 p.Asp1152His ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu967Ser ABCC7 p.Ser912Leu ABCC7 p.Gly1244Val ABCC7 p.Ile752Val The more recent estimates provide much lower values, ranging from 1:5000 [14], 1:6000 cited in WHO 2002 report [15] to 1:7500 for Southeastern Poland estimated for a 1-year period of 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 15 17 L967S 0.27 c.2900T.C 3032T.C 1 CFMDB; rs1800110 unknown 18 21 D1152H 0.50 c.3454G.C 3586G.C 1 CFMDB; rs75541969 F508del Sequence changes considered as lacking pathogenic effect 4 4 I148T 2.04 c.443T.U 575T.U 4 IL19e unknown 13 14 I752V 0.35 c.2254A.G 2386A.G 1 Novelf F508 15 17 S912L 2.12 c.2735C.T 2867C.T 1 CFMDBg ; rs121909034 F508 Legend: a IL19 i 17 - mutations included in the INNOLiPA tests (see below); CFMDB - non-INNOLiPA mutations present in the CTFR mutation database; novel - mutations first reported in this study; b in three chromosomes R668C with G576A in trans; c F508del, c.1585-1G.A, G542X, N1303K or c.579+3A.G; d F508del, G542X, R553X or N1303K; e not pathogenic if not in cis with c.3067-72del6 (l.n.3199del6); f not pathogenic - see explanation the text; g not pathogenic if not in cis with G1244V. Login to comment 102 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser1251Asn ABCC7 p.Ile148Thr ABCC7 p.Arg560Thr ABCC7 p.Gln552* a Mutations detected by two INNOLiPA_CFTR tests (legacy names): IL19 (INNOLiPA_CFTR19): F508del; G542X; N1303K; W1282X; G551D; 1717-1G.A; R553X; CFTRdele2,3(21kb); I507del; 711+1G.T; 3272-26A.G; 3905insT; R560T; 1898+1G.A; S1251N; I148T; 3199del6; 3120+1G.A; Q552X. Login to comment 103 ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Glu60* IL17 (INNOLiPA_CFTR17_TnUpdate): 621+1G.T; 3849+10kbC.T; 2183AA.G; 394delTT; 2789+5G.A; R1162X; 3659delC; R117H; R334W; R347P; G85E; 1078delT; A455E; 2143delT; E60X; 2184delA; 711+5G.A; polymorphism 5T/7T/9T. Login to comment 121 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly314Arg Three mutations in our reduced data set were significantly (p,0.03) less frequent than in Warsaw (F508del: 67.2% vs 71.8%; G542X: 1.98% vs 2.92%; N1303K: 1.47% vs 2.92%), while two mutations were significantly more frequent (c.3468+2_3468+3insT: 0.86% vs 0.10%; c.489+1G.T: 0.43% vs 0%; G314R: 0.34% vs 0%). Login to comment 137 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1158* ABCC7 p.Arg668Cys ABCC7 p.Arg117Cys ABCC7 p.Glu92Lys ABCC7 p.Ile336Lys ABCC7 p.Arg851* ABCC7 p.Gly314Arg ABCC7 p.Arg153Ile Mutations a Poland Czechs Slovakia c Germany Lithuania W. Ukraine E. Hungary Romania c Bulgaria Serbia Greece Number of chromosomes 1476 1200 856 700 98 264 80 256 208 352 874 F508del 54.54 b 67.42 d 66.80 d 72.00 d 52.0 54.17 70.00 56.3 65.38 d 72.28 d 53.40 exon2,3del21kb (l.n.CFTRdele2,3_21kb) 4.47 5.75 2.26 1.2 f 2.0 4.17 5.00 1.6 NA 0 e 0.34 e c.3717+12191C.T (l.n.3849+10kbC.T) 3.93 1.67 e 4.28 1.00 e NA 0.76 0 0.4 e 1.44 0 e 0.11 e c.2012delT (l.n.2143delT) 1.83 0.92 1.10 0.71 0 1.14 0 0 e 0 0 e 0 e c.1585-1G.A (l.n.1717-1G.A) 1.83 0.33 e NA 0.86 0 0.38 1.25 0.4 0 0 e 0 e G542X 1.69 2.00 4.06 d 1.43 0 2.65 3.75 3.9 3.37 2.57 3.90 d R347P 1.57 0.92 1.10 1.57 0 0 1.25 NA 1.44 0 e 0.11 e N1303K 1.22 2.42 2.03 2.29 2.0 4.92 d 5.00 0.8 6.73 d 0 2.63 c.2052-2053insA (l.n.2184insA) 1.02 0.42 1.58 0.57 0 7.20 d 5.00 d 0 0.48 0.28 0 e R553X 0.95 0.50 0.90 2.29 4.2 d 0.38 0 NA 0 0 0 c.3468+223insT (l.n.3600+2insT) 0.75 0.25 NA 0 e 0 NA 0 NA 0 0 0 e c.2051-2052AA.G (l.n.2183AA.G) 0.68 0.08 NA 0.57 0 0.38 0 0.8 0 0 1.38 W1282X 0.61 0.58 0.50 0.71 1.0 2.27 0 2.3 d 0.96 0 0.67 c.3140-26A.G (l.n.3272-26A.G) 0.61 0.67 0.50 0.86 0 0.76 0 0.4 0 0 0.81 l.n.IVS8 T 5 _TG 12-13 0.54 NA NA NA 0 NA NA NA NA 0 NA R334W 0.41 0.25 NA 0.29 0 0.76 0 0.4 0 0.28 0.81 c.1766+1G.A (l.n.1898+1G.A) 0.41 1.42 d 0.50 0 0 1.14 0 NA 0 0 0.11 c.489+1G.T (l.n.621+1G.T) 0.34 0.42 NA 0.14 0 0.76 0 0.8 0 2.86 d 5.72 d R117H 0.34 NA NA 0.29 0 0 0 0.4 0 0 0.23 G551D 0.34 2.91 d 0.50 1.00 0 0 0 0 0 0 0.34 G314R 0.37 0 NA 0 0 0 0 NA 0 0 0 R668C 0.34 0 NA 0 0 0 0 NA 0 0 0 c.3528delC (l.n.3659delC) 0.27 0.17 NA 0.57 0 0 0 NA 0 0 0 c.164+1G.A (l.n.296+1G.A) 0.20 0.08 NA 0 0 0 0 NA 0 0 0 R851X 0.20 0.08 NA 0 0 0 0 NA 0 0 0 I336K 0.14 0.58 NA 0.45 0 0 0 NA 0 0 0 R1158X 0.14 0.08 NA 0 0 0 0 NA 0 0 1.03 E92K 0.14 0.08 NA 0 0 0.38 0 NA 0 0 0 R153I 0.14 0 NA 0 0 0 0 NA 0 0 0 c.579+3A.G (l.n.711+3A.G) 0.14 0.17 NA 0 0 0 0 NA 0 0 0.69 c.2589-2599del11bp (l.n.2721- 31del11bp) 0.14 0.08 NA 0 0 0.38 0 NA 0 0 0 I507del 0.14 0.08 NA 0.15 0 0 0 0 0 0.28 0.69 R117C 0.14 0.08 NA 0.15 0 0 0 NA 0 0 0.23 of mutation panels [20]), listed in Table 4, were compared to those reported for several Central and Southeastern European countries [21-29]. Login to comment 143 ABCC7 p.Trp1282* The frequency of Israeli c.3717+12191C.T (l.n.3849+10kbC.T) [4] was significantly elevated in Poland (3.9%) and Slovakia compared to most of the examined populations (Czechs, Germany, Romania, Serbia, Greece, p,0.005), possibly indicating the Ashkenazi-Jewish contribution; in contrast, the frequency of another Israeli mutation, W1282X [4,12], was significantly lower in Poland (0.61%) than in Romania (p,0.006). Login to comment 145 ABCC7 p.Asn1303Lys The frequency of Mediterranean c.1585-1G.A (l.n.1717-1G.A) [4-5] was 1.83%, significantly (p,0.005) higher than in several other Slavic populations, while that of another Mediterranean mutation, N1303K [4], was 1.22%, significantly (p,0.005) lower than in Western Ukraine, Bulgaria, Serbia and Hungary. Login to comment 150 ABCC7 p.Gly314Arg G314R, a novel missense change found in 0.37% of the studied CF chromosomes, might be another PL founder mutation. Login to comment 151 ABCC7 p.Gly314Arg These observations would have to be confirmed by screening for c.3468+2_3468+3insT and G314R in a larger numbers of CF patients from other neighboring European populations. Login to comment 152 ABCC7 p.Arg117His The relatively high frequency (0.54%) of IVS9 T5_TG12-13 (without R117H in cis) in PL patients could not be compared with other populations. Login to comment 153 ABCC7 p.Arg117His While TG12-13 in cis with T5 are known to contribute to less efficient splicing of exon 10 and to abnormal phenotype [31-32], most of the CF tests do not determine the length of the TG repeat, and reporting the T5 in intron 9 (l.n.IVS8-T5) as a pathogenic mutation has been recommended only if in cis with R117H [12]. Login to comment 154 ABCC7 p.Gln1412* ABCC7 p.Phe311Leu Table 4. Cont. Mutations a Poland Czechs Slovakia c Germany Lithuania W. Ukraine E. Hungary Romania c Bulgaria Serbia Greece Number of chromosomes 1476 1200 856 700 98 264 80 256 208 352 874 F311L 0.14 0 NA 0 0 0 0 NA 0 0 0 Q1412X 0.14 0 NA 0 0 0 0 NA 0 0 0 Other reported 1.52 8.51 NA 7.10 2.0 1.14 7.50 3.8 12,03 4.28 17.83 Not detected 17.5 0.50 13.89 4.57 35.8 16.29 6.25 27.7 8.17 17.43 9.15 Estimated efficiency of INNOLiPA tests 75.5 89.9 84.0 88.7 61.2 74.6 87.5 69.1 80.3 78.7 73.3 Legend: Data are given in %. Login to comment