TO: MEMBERS OF THE CYSTIC FIBROSIS GENETIC ANALYSIS CONSORTIUM

Amos, Boston U, USA Jaume-Roig, Son Dureta, Spain

Anvret, Stockholm, Sweden Kalaydjieva, Sofia, Bulgaria

Barker, U Alabama Birm, USA Kant, U Penn, USA

Barton, Cambridge, England Kitzis, CHU-Paris, France

Beaudet, Baylor, USA Klinger, Integ Genet, USA

Baranov, Leningrad, USSR Komel, Ljubljiana, Yugoslavia

Boué, Paris, France Knight, London, England

Cao, U Cagliari, Italy Krueger, Hahnemann, USA

Carbonara, Torino, Italy Lavinha, Lisboa Codex, Portugal

Cassiman, U Leuven, Belgium Lissens, Vrije U Brussels, Belgium

Claustres, Montpellier, France Loukopoulos, Athens, Greece

Cochaux, Brussels, Belgium Lucotte, College de France

Collins, U Michigan, USA Malcolm, ICH-London, England

Coskun, Hacettepe U, Turkey Malik, Basler-Basel, Switzerland

Coutelle, East Berlin Mao, Collab Res, USA

Cutting, Johns Hopkins, USA McIntosh, WGH-Edinburgh, Scotland

Dallapiccola, Roma, Italy Morel, Lyon, France
De Arce, Dublin, Ireland Morgan, McGill, Canada

de la Chapelle, Helsinki, Finland Nukiwa, Tokyo, Japan

Dean, NCI Frederick, USA Ober, U Chicago, USA

Desnick, Mount Sinai, New York, USA Olek, U Bonn, West Germany

Edkins, Perth, Australia Orr, U Minnesota, USA

Edwards, Oxford, England Pignatti, U Verona, Italy

Efremov, Skopje, Yugoslavia Ramsay, SAMIR, South Africa

Elles, St Mary's-Manchester, England Richards, GeneScreen, USA

Erlich, Cetus, USA Romeo, Gaslini-Genoa, Italy

Estivill, Barcelona, Spain Rowley, Rochester, USA

Ferec, Brest, France Rozen, Montreal Children, Canada

Ferrari, Milano, Italy Scheffer,UGroningen,The Netherlands

Gerard, Harvard, USA Schmidtke, IHG, Berlin

Gilbert, Cornell, New York, USA Schwartz, U Copenhagen, Denmark

Godet, Villeurbanna, France Sebastio, Naples, Italy

Goossens, Creteil, France Seltzer, U Colorado, USA

Graham, Belfast, N Ireland Spona, Vienna, Austria

Halley, Rotterdam, The Netherlands Super, Royal Manchester, England

Harris, Guy's-London, England Thibodeau, Rochester, USA

Higgins, Birmingham, England Tümmler, Hannova, West Germany

Highsmith, NC Mem Hosp, USA Verellen-Dumoulin,Bruxelles,Belgium

Hood, California Inst Tech, USA Willems, U Antwerp, Belgium

Horst, Münster, West Germany Williamson,St Mary'sLondon,England

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FROM: LAP-CHEE TSUI TOTAL NUMBER OF PAGES: 4

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NEWSLETTER #26, September 14, 1990

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1. Jones C, McIntosh and Brock report a mutation in exon 10 (C524X); see attached letter.

2. Bozon D, Zielenski J, Rininsland F, Rommens J and Tsui L-C report a sequence alteration at nucleotide position 129 where G is replaced by C (129G->C). This change is actually upstream of the proposed initiation codon, at position -4. It was first found on the father's CF chromosome in Toronto family #14 and associated with haplotype IIa. The CF children in this family are PS and the maternal CF chromosome carries [[Delta]]F508. We examined 85 non-[[Delta]]F508 CF chromosomes (including 10 from group II) and found 2 additional examples. Interestingly, these 2 chromosomes were also found in 2 unrelated PS patients with the other chromosome carrying [[Delta]]F508 but, unfortunately, their haplotype was not determined. This mutation was not detected in 51 normal chromosomes (including 43 group II). While it is not entirely clear whether 129G->C causes CF, it is possible that it reduces the expression of CFTR. There may be a mutation elsewhere in this allele, but no other change was found after sequencing over 95% of the coding and immediately flanking introns. To detect this change, ASO hybridization may be performed with N oligo (5'GCC CAG AGA CCA TGC A) and mutant oligo (5'GCC CAG ACA CCA TGC A) and washing at 49[[ring]] in 2xSSC; genomic DNA may be amplified with primers B115B and 10D.

3. The correct designaton for the mutation reported by Highsmith et al in the last issue of newsletter should be 2789+5G->A (not 2751).

4. For those members who have trouble receiving the previous Newsletters by FAX, you will receive them (issues #14-#26) in the mail shortly. If you notice any mistakes in those issues, please drop me a note. If you want a copy of the compiled issues #1-#13, please also let me know.

5. The time slot for the general meeting of the Consortium has been allocated. It will be from 8 pm to 10 pm on Thursday, October 4 (during the next International CF Congress in Arlington, Virginia, USA). The meeting room has yet to be determined.

6. I will try to compile a last minute report about the population distribution of each mutation before the general meeting. Please send in your data as soon as possible.

Best regards,

Lap-Chee Tsui

Standardized population screening report to the consortium

From (Name of principal investigator): ___________________________

Patient population (Location / ethnic origin):

# CF chrom. # CF chrom.

Name Total (*) w/ mut'n Name Total (*) w/ mut'n

1. [[Delta]]F508 ______ ______ 31. Y913C ______ ______

2. [[Delta]]I507 ______ ______ 32. R553Q ______ ______

3. 2566insAT ______ ______ 33. S549R(A->C)______ ______

4. F508C (var?)______ ______ 34. P574H ______ ______

5. I506V (var) ______ ______ 35. 1154insTC ______ ______

6. G551D ______ ______ 36. 1214delT ______ ______

7. S549N ______ ______ 37. 3659delC ______ ______

8. R553X ______ ______ 38. 556delA ______ ______

9. A559T ______ ______ 39. 621+1G->T ______ ______

10. G542X ______ ______ 40. E1371X ______ ______

11. S549R(T->G)______ ______ 41. G85E ______ ______

12. R560T ______ ______ 42. R851X ______ ______

13. A455E ______ ______ 43. 711+1G->T ______ ______

14. Q493X ______ ______ 44. G179R ______ ______

15. R117H ______ ______ 45. 2909delT ______ ______

16. D110H ______ ______ 46. 2522insC ______ ______

17. R347P ______ ______ 47. R1162X ______ ______

18. S1255X ______ ______ 48. Q1291H ______ ______

19. W1282X ______ ______ 49. Q39X ______ ______

20. W1316X ______ ______ 50. G1244E ______ ______

21. 444delA ______ ______ 51. Y1092X ______ ______

22. 3821delT ______ ______ 52. 3662delA ______ ______

23. R334W ______ ______ 53. 1677delA ______ ______

24. S549I ______ ______ 54. V520F ______ ______

25. G458V ______ ______ 55. 3732delA ______ ______

26. G1349D ______ ______ 56. 2789+5G->A______ ______

27. W846X ______ ______ 57. C524X ______ ______

28. 1717-1G->A______ ______ 58. 129G->C var?_____ ______

29. N1303K ______ ______ ______ ______

30. Y563N ______ ______ ______ ______

(*) In order to have a more useful number for comparison among the different populations, please include the number of [[Delta]]F508 screened for the non-[[Delta]]F508 mutations, even though you might not have done so.