ABCMdb

PMID: 9788722

Petreska L, Koceva S, Plaseska D, Chernick M, Gordova-Muratovska A, Fustic S, Nestorov R, Efremov GD
Molecular basis of cystic fibrosis in the Republic of Macedonia.
Clin Genet. 1998 Sep;54(3):203-9., [PubMed]

Sentences

No. Mutations Sentence Comment

40 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Trp1316* ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln359Lys The screening procedures of 17 other known CF mutations included detection of mutations in the PCR products of positive controls and samples by: a) direct analysis on PAGE for A1507 and 1677delTA, simultaneously to AF508; b) hybridization with ASOs for mutation R117H (21), 1717-1GdA (22), G542X (22), N1303K (23), and W1316X (24), and c) restriction digestion `followed by agarose or polyacrylamide gel electrophoresis (exon 3 PCR product digested with HinfI for CUE, exon 4 with HinfI for 444delA, exon 5 with RsaI for 711 + 5G --*A,exon 7 with HhaI for R347H or with RsaI for Q359K/T360, exon 11 with HincII for both G551D and R553X, exon 19 with DdeI for R1162X or with HphI for 3849G+A, a 175 bp PCR fragment of exon 13 with HaeIII for 2556insAT) (4). Login to comment 65 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Only G542X and N1303K were found among the 17 more common mutations that, besides AF508, were screened by direct detection. Login to comment 68 ABCC7 p.Val1397Glu Two of them were found by SSCP: 711+3A +G mutation, found in two Albanian chromosomes associated with haplotype A, and V1397E mutation found in a Macedonian chromosome. Login to comment 70 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Frequency of mutations identified in CF chromosomesfrom the Republic of Macedonia Mutation (location) Number of chromosomeswith mutation Ethnic group (fraction%) Method of detection XV-2clKM19 haplo- References (96) type AF508 (exon 10) 79 (47.6) All groups 12% PAGE BD (3) G542X (exon 11) 6 (3.6) All groups Dot blot B (22) N1303K (exon 21) 3 (1.8) MKa(2.8%) Dot blot B (23) 621t l G + T 2 (1.2) MK (1.9%) SSCP B (30) fintron 4) (intron 5) (exon 19) (exon 4) (intron 11) 711t3A-rG 2 (1.2) ALb (3.8%) SSCP A (31)c 384% +A 2 (1.2) MK (1.9%) SSCP C (32) 457TAT+G 1 (0.6) MK (0.9%) SSCP B (33) 1811+1G-.C l(0.6) MK (0.9%) DGGE 8 Hphl dig. Login to comment 71 ABCC7 p.Val1397Glu C (19Y V1397E (exon 23) (0.6) MK (0.9%) SSCP ND (31)' Total 97 (58.4) a MK, Macedonian; AL, Albanian; novel mutation identified during this study 205 al. Table . Login to comment 72 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Val1397Glu Clinical feaiures of the CF patients from Macedonia Genotype Number of CF patients (%) PI PS Shwachman scorea Age of onset GI- (mmljl) NDb AF508/AF508 AF508/G542X AF508/N1303K AF508/711+3A-.G AF508/711+W+G AF508/621+lG+T AF508/621+1G+T AF508/1811+1G-*C AF508/457TAT-*G AF508/3849G+A G542X/3849G+A N1303K/ND V1397E/ND AF508/ND NDiND Total 26 (31.3) 5 (6.0) 2 (2.4) 2 (2.4) 2 (2.4) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2) 13 (15.7) 27 (32.5) 83 (100.0) 26 5 2 1 1 1 1 1 1 1 1 1 7 4 1 15 7 63 13 25-85 30-60 38 84 82 35 78 80 83 50 82 83 I 30-60 20-90 ~~~~~ 1-6 months 1 month 3 months 1 month 1 month 2 months 2.5 years 2 months 2 months 2 months 1 month 6 years 3 weeks Variable Vanable ~ ~ ~~~ 80-210 116-166 180-200 80 120 170 156 240 150 98 190 65 65 65-2300 2 65-130 (ps) 58-230 (PO 5 65-130 (PS) 7 a Shown is the most recent Shwachman score. Login to comment 75 ABCC7 p.Arg75Gln ABCC7 p.Leu467Pro In a total of 23 CF and five undetermined chromosomes we characterized nine CFTR gene polymorphisms: a) by SSCP: R75Q (30), 405 +46GJT (34), 875+40A/G (35), L467P and 4002A/G (4), M470V (22), and the new one P324P (18); b) by CDGE: T966T (36) and 3041-92G/A (37). Login to comment 78 ABCC7 p.Leu467Pro The L467P polymorphism was found on three AF508 chromosomes. Login to comment 79 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* Genotype-phenotype data Nine different genotypes were observed in 41/83 (49.4%) unrelated families: AF508/AF508 (n =26), AF508/457TAT-,G (n = l), AF508/621+1G+T (n = 2), AF508/G542X (n = 5), AF508/N1303K (n =2), AF508/38496-,A (n= I), G542X/ 384963 A (n = l), AF508/711 +3A G (n = 2), AF508/1811+1G-C (n = 1). Login to comment 80 ABCC7 p.Val1397Glu In two families the genotypes were N1303/unknownand V1397E/unknown. Login to comment 98 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* They include the 'oldest` G542X (found in different ethnic groups) and N1303K mutations (found only among Macedonians), and one additional mutation, 621 +lG+T, that is among the world`s most common CF alleles. Login to comment 99 ABCC7 p.Gly551Asp ABCC7 p.Arg553* Mutations that are frequent in Bulgaria (1677delTA) (1l), and Serbia (G551D, R553X) (5, 10) were not found in this study. Login to comment 101 ABCC7 p.Val1397Glu The mutations 711 +3A+G, 1811+IG-tC and V1397E were described for the first time in the literature, and to our knowledge they have not been found outside Macedonia. Login to comment