TO: MEMBERS OF THE CYSTIC FIBROSIS GENETIC ANALYSIS CONSORTIUM

Amos, Boston U, USA Highsmith, NC Mem Hosp, USA

Anvret, Stockholm, Sweden Horst, Münster, West Germany

Barker, U Alabama Birm, USA Jaume-Roig, Son Dureta, Spain

Barton, Cambridge, England Kalaydjieva, Sofia, Bulgaria

Beaudet, Baylor, USA Kant, U Penn, USA

Baranov, Leningrad, USSR Kitzis, CHU-Paris, France

Boué, Paris, France Klinger, Integ Genet, USA

Bowcock, Stanford, USA 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 Olek, U Bonn, West Germany

Desnick, Mount Sinai, New York, USA Orr, U Minnesota, USA

Edkins, Perth, Australia Pignatti, U Verona, Italy

Edwards, Oxford, England Ramsay, SAMIR, South Africa

Efremov, Skopje, Yugoslavia Richards, GeneScreen, USA

Elles, St Mary's-Manchester, England Romeo, Gaslini-Genoa, Italy

Erlich, Cetus, USA Rowley, Rochester, USA

Estivill, Barcelona, Spain Rozen, Montreal Children, Canada

Ferec, Brest, France Scheffer,UGroningen,The Netherlands

Ferrari, Milano, Italy Schmidtke, IHG, Berlin

Gerard, Harvard, USA Schwartz, U Copenhagen, Denmark

Gilbert, Cornell, New York, USA Sebastio, Naples, Italy

Godet, Villeurbanna, France Seltzer, U Colorado, USA

Goossens, Creteil, France Spona, Vienna, Austria

Graham, Belfast, N Ireland Super, Royal Manchester, England

Halley, Rotterdam, The Netherlands Thibodeau, Rochester, USA

Harris, Guy's-London, England Tümmler, Hannova, West Germany

Higgins, Birmingham, England Verellen-Dumoulin,Bruxelles,Belgium

Willems, U Antwerp, Belgium

Williamson,St Mary'sLondon,England

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FROM: LAP-CHEE TSUI TOTAL NUMBER OF PAGES: 22

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NEWSLETTER #23, August 9, 1990

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1. Gasparini P, Savoia A, Bonizzato A, Dognini M and Piagnati PF report a nonsense mutation (R1162X) at nucleotide position 3616 (C to T) in exon 19. The same group report a frequent silent mutation at nucleotide position 4521 (G or A) in exon 24 (see letter).

2. McIntosh I, Shrimpton T, Jones C and Brock D report a missense or splice mutation (Q1291H) at nucleotide position 4005 (G to C) in exon 20 (see letter).

3. Cutting GR and Curristin S report a nonsense mutation (Q39X) at nucleotide position 247 (C to T) in exon 2 (see letter).

4. Romeo G, Ronchetto P, Devoto M, Goossens M, Fanen P and Vidaud M report a missense mutation (G1244E) at nucleotide position 3863 in exon 20 (see letter).

5. Bozon D, Zielenski J and Tsui L-C report a nonsense mutation (Y1092X) at nucletoide position 3408 (C to A) in exon 17b. It was found in Toronto family #34 on a haplotype group IIa chromosome from the mother. It was not found in 52 other CF chromosomes (6 of haplotype IIa) nor 50 N chromosomes (44 of haplotype IIa). The mutation destroys a RsaI site. Digestion of the PCR product generated from primers 17ai5 and 17ai3 should yield 4 fragments (204, 95, 85 and 79) for the normal sequence and 3 fragments (299, 85 and 79) for the mutant.

6. A table summarizing all the mutations reported to date is attached. Please let me know if there is any error and if any of the work (ie. those listed as per.comm.) has been accepted (or, if you wish to list, submitted).

7. The mutation screening table has also been compiled (see attached). I realize that there are still numerous errors; for example, there should be at least 1 CF chromosome under each mutation but there are a few left with zero. Also, the total number of CF chromosomes screened is not very reliable; I think one should pay more attention to the numbers found. If there is any major discrepancy, please let me known as soon as possible. In any case, the purpose of this table is to provide some guidelines for those who are planning to screen their respective populations.

8. I have asked Chris Higgins to go ahead with his CFTR model with annotations of the various mutations, because I have not heard any objection from you.

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 ______ ______ ______ ______

23. R334W ______ ______ ______ ______

24. S549I ______ ______ ______ ______

25. G458V ______ ______ ______ ______

26. G1349D ______ ______ ______ ______

27. W846X ______ ______ ______ ______

28. 1717-1G->A______ ______ ______ ______

29. N1303K ______ ______ ______ ______

30. Y563N ______ ______ ______ ______