S28 Supplement / The Netherlands Journal of Medicine 54 (1999) S3 –S84 ´ revealed. The underlying mechanism causing this insertion is a with MI (details in Fialova et al. – this meeting), thus raising the duplication of these five nucleotides. Since this results in a total detection rate to 95.7%. Screening for this mutation in other frameshift introducing a STOP-codon at amino acid position 528 populations might elucidate its ethnic origin / spread and similarly of the transcript, this novel mutation causes loss of function of the help to increase their total mutation detection rates. CFTR protein. Supported by IGA: 2056-5, 2899-5, 3526-3, 4124-3; OK192. 21. Molecular diagnosis of cystic fibrosis in Yugoslavian 19. Screening for CF mutations in Russian population. N.V. 1 1 2 population. D. Radivojevic , M. Guc-Scekic , E. Kanavakis , J. Petrova, E.K. Ginter. Research Centre for Medical Genetic, 1 2 2 1 1 Savic , M. Tzetis , T. Antoniadi , P. Minic , M. Djurisic , T. Moscow, Russia. 1 1 1 Lalic , A. Cvetkovic . Mother and Child Health Institute of 435 CF patients having been treated in the department of 2 Serbia, Belgrade, Yugoslavia, Choremio Research Lab., St. mucoviscidosis of our Centre have been screened for 16 CF Sophia’ s Children’ s Hospital, Athens, Greece. mutations. Above 80% of patients were from the European part of The isolation of cystic fibrosis (CE) gene at the CF locus Russia and the others were from the Siberia and some other assigned to the long arm of the chromosome 7 band q31 and regions of the UIG. 12 of 16 mutations have been identified in definition of it’s protein product named CFTR permits to under- studied CF chromosomes, their relative frequencies are as follows: stand the basic defect in this inherited disorder. To initiate the dF508–53.5%; 394delTT–0.6; R334W–0.8; 1677delTA–0.5; complete characterization of mutations in the CFTR gene in G542X–1.7; G551D–0.1; 2143delT–2.0; 2184insA–2.0; Yugoslavian CF patients, we screened 108 patients for CF S1196X–0.6; W1282X–1.8; N1303K–2.7; 3849 1 10kbC-T–1.7. mutations using methods of polyacrilamide and denaturing gra- Mutations R347P, dI507, 621 1 1G-T, R553X have not been dient gel electrophoresis. Four different mutations (DF508, detected. These mutations account for about 70% of all CF G542X, 621 1 1G . A and S466X) accounted for 81.94% of the chromosomes. About 30% of CF alleles remain to be identified in CF alleles, of which the DF508 mutation had a frequency of Russian population. We have studied the association between CF 75.46%. Other 13 mutations (R334W, 2184insA, D1507, 1525- mutations and haplotypes of three markers (XV2c / KM19 / GATT 1G . A, E585X, R75X, R297Q, 2789 1 5G . A, 457TAT . G, VNTR in 6a intron). 95% of dF508 chromosomes are associated 582insG, R1070Q, A120T and 2907delTT), already described, with haplotype B6 and 5% – with D6. G542X, 2143delT, N1303K accounted for another 5.98% of CF alleles. A new mutation mutations are associated with haplotype B6; N1303K mutation has (2723delTT) was found in one CF patient (compound been also identified on chromosome with A6 haplotype. Mutations heterozygote for DF508 and 2723delTT). Thus, so far, identified 2184insA and S1196X have been found on chromosomes with mutations in the CFTR gene in Yugoslavian CF patients account D7; W1282X – with B7; 1677delTA – with A7. More than 60% for 88.38% of the CF alleles. During this period of investigation, of CF chromosomes with unidentified mutations are associated 29 families applied for prenatal diagnosis and as a result, 22 with haplotypes A7 and C7; so we consider that so-called specific healthy babies were born. ‘‘Russian’’ (or Slavonic) CF mutations should be searching in the group with these haplotypes. 22. Regional distribution of CFTR mutations in central Italy. 1 2 2 Teresa Repetto , Elisabetta Pelo , Fiammetta Sbernini , 2 2 2 20. A high frequency of the CFTRdel21kb mutation in the Giovanni Taccetti , Barbara Minuti , Lore Marianelli , Fran- 2 1 Czech population raises the total detection rate to over 95%. cesca Torricelli . Cystic Fibrosis Regional Meyer Hospital, 1 1 1 1 2 ´ ´ ´ ´ A. Krebsova , M. Fialova , I. Sakmaryova , M. Holova , B. Florence, Italy, Cytogenetic and Genetic Unit of Careggi 2 3 4 1 1 ¨ ´ ´ Mercier , H. Cuppens , T. Dork , V. Vavrova , M. Macek , M. Hospital, Florence, Italy. 1 1 2 Macek Jr. , CF Cntr, UH-Motol, Prague, Czech Rep., ETSBO, Cistic fibrosis is one of the most common severe autosomal 3 4 Brest, France, Cntr. Med. Genet., U. Leuven, Belgium, IHG, recessive disorders in caucasian, it affects 1 / 2.500 live births MH Hannover, Germany. although the estimated prevalence shows substantial regional In a group of 248 Czech CF patients we initially detected: variation. More than 700 mutations have been reported by DF508-71.6% (355 / 496 of all CF chromosomes), G551D-4.0% members of the genetic analysis. The Italian population showed (20), N1303K-3.0% (15), G542X-2.2% (11), R347P-0.8% (4), patterns of genetic differentiation that were interpreted as being W1282X-0.6% (3); 1717-1G → A, R1162X, 3849 1 10kbC → T- the result of population settlement going back to pre-Roman time. 0.4% (2) each; 2789 1 5G → A, R334W, R553X, Y122X, 621 1 Geographic analysis of CF mutation relative frequencies in Italy 1G → T, G85E-0.2% (1) each 5 84.6%. DGGE analysis (Hum showed a genetic heterogeneity among Italian regions. Northern Mut 9:136) revealed: 1898 1 1G → A-2.0% (10), 2143delT-1.2% regions are well differentiated from central-southern region. (6); 4374 1 1G → T, E92X, 2184insA-0.4% each (2); Central Italy a more blurred pattern of CFTR mutations. The 12 2183delAA → G, S1118F, M952L, V1212I, L720F, Y122X, most frequent mutations characterize about 81% of CF chromo- I336K, 185 1 1C → T, S495L, 3944delGT, S42F-0.2% (1) each some in North Italy while only 69% in central Italy (62% (novel alleles) 5 6.2%. Finally, the CFTRdel21kb allele (non- Tuscany). A sample of 176 CF Tuscany patients was collected; detectable by DGGE, SSCA etc.) accounted for 4.6% (23). It is the 352 chromosome of this patients are analyzed early for 14 our 2nd most common ‘‘severe’’ mutation, significantly associated mutations following for other mutations (31 total mutations).