TO: MEMBERS OF THE CYSTIC FIBROSIS GENETIC ANALYSIS CONSORTIUM

Amos, Boston U, USA Kant, U Penn, USA

Anvret, Stockholm, Sweden Kitzis, CHU-Paris, France

Barker, U Alabama Birm, USA Klinger, Integ Genet, USA

Barranger, Los Angeles, USA Knight, London, England

Barton, Cambridge, England Lavinha, Lisboa Codex, Portugal

Beaudet, Baylor, USA Lissens, Vrije U Brussels, Belgium

Boué, Paris, France Loukopoulos, Athens, Greece

Bowcock, Stanford, USA Lucotte, College de France

Cao, U Cagliari, Italy Malcolm, ICH-London, England

Carbonara, Torino, Italy Malik, Basler-Basel, Switzerland

Cassiman, U Leuven, Belgium Mao, Collab Res, USA

Claustres, Montpellier, France McIntosh, WGH-Edinburgh, Scotland

Collins, U Michigan, USA Morel, Lyon, France

Cutting, Johns Hopkins, USA Morgan, McGill, Canada

Dallapiccola, Roma, Italy Naylor, UT San Antonio, USA

De Arce, Dublin, Ireland Olek, U Bonn, West Germany

Dean, NCI Frederick, USA Orr, U Minnesota, USA

Desnick, Mount Sinai, New York, USA 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,TheNetherlands

Ferrari, Milano, Italy Schmidtke, IHG, Berlin

Godet, Villeurbanna, France Schwartz, U Copenhagen, Denmark

Goossens, Creteil, France Sebastio, Naples, Italy

Graham, Belfast, N Ireland Seltzer, U Colorado, USA

Gruenert, UCSF, USA Spona, Vienna, Austria

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

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

Highsmith, NC Mem Hosp, USA Tümmler, Hannova, West Germany

Horst, Münster, West Germany Verellen-Dumoulin,Bruxelles,Belgium

Jaume-Roig, Son Dureta, Spain Willems, U Antwerp, Belgium

Kalaydjieva, Sofia, Bulgaria Williamson,St Mary'sLondon,England

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FROM: LAP-CHEE TSUI TOTAL NUMBER OF PAGES:

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NEWSLETTER #19, June 18, 1990

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1. This newsletter is the first one after May 19. There has not been much to report. But, I should apologize for my slight delay in sending the following information.

2. Dean, White, Gerrard and Stewart have reported a nonsense mutation in exon 14A (R851X); they have also supplied the SSCP protocol (see attached).

3. We (Zielenski, Bozon, Kerem and Tsui) have found 2 other mutations and 1 sequence polymorphism:

711+1G->T- This G to T switch occurs at the splice junction after exon 5. The mutation is found on the mother's CF chromosome (group IIb) in family #22, a French Canadian family from Chicoutimi. The other mutation in this family is 621+1G->T. We checked 54 CF chromosomes (9 from group II) and 49 N chromosomes (41 group II), but did not see another example. To detect this mutation, genomic DNA may be amplified by PCR with primers 5i5' and 5i3' and hybridized with ASOs; N is 5'-GGT ACA TAC TTC ATC A-3' and mutant is 5'-GGT ACA TAA TTC ATC A-3'; final stringent wash is 2xSSC at 40[[ring]].

G179R- This Gly to Arg missense mutation in exon 5 is due to a G to A change at nucleotide position 664. The mutation is found on the mother's CF chromosome (group 5) in family #50; the other mutation in this family is [[Delta]]F508. We have not found another example so far after screening 61 CF chromosomes (including 1 from group 4 and 2 others from groups 5) and 54 N chromosomes (including 4 group 4 and 5 group 5). To detect this mutation, genomic DNa may be amplified by PCR with primers 515' and 513'; the ASO for normal sequence is 5'-AAG TAT TGG ACA ACT T-3' and the ASO for the mutant is 5'-AAG TAT TAG ACA ACT T-3'; final washing is at 37[[ring]] with 2xSSC.

Polymorphism at nucleotide position 356 (C/T) in exon 3. There is a corresponding change of the encoded amino acid from Arg to Gln at position 75. We found 5 normal chromosomes of haplotype IIa with T (Gln) at that position among 33 examined (16 of them were IIa). 5/38 = 13%. We also checked 41 CF chromosomes (23 from IIa) but none has the change.

4. Garry Cutting have asked me to distribute a draft of the consortium report on G551D. Please direct any corrections, suggestions or new data to Garry at FAX# (301) 955-0484. He is still collecting phenotype data on patients with the G551D mutation.

5. We are in the final stages of compiling all the mutation screening results- it is a large table! Hopefully, we will have it by the end of this week.

Best regards,

Lap-Chee Tsui

Standardized population screening report to the consortium

From (Name of principal investigator): ___________________________

Patient population (Location / ethnic origin):

(use different sheets for different populations)

Number of CF chromosomes

Name Total screened with the mutation Other comments

(* indicate if only non-[[Delta]]F chromosomes are screened)

1. [[Delta]]F508 ___________ ___________ __________________

2. [[Delta]]I507 ___________ ___________ __________________

3. 2566insTT ___________ ___________ __________________

4. F508C (var?)___________ ___________ __________________

5. I506V (var) ___________ ___________ __________________

6. G551D ___________ ___________ __________________

7. S549N ___________ ___________ __________________

8. R553X ___________ ___________ __________________

9. A559T ___________ ___________ __________________

10. G542X ___________ ___________ __________________

11. S549R(T->G)___________ ___________ __________________

12. R560T ___________ ___________ __________________

13. A455E ___________ ___________ __________________

14. Q493X ___________ ___________ __________________

15. R117H ___________ ___________ __________________

16. D110H ___________ ___________ __________________

17. R347P ___________ ___________ __________________

18. S1255X ___________ ___________ __________________

19. W1282X ___________ ___________ __________________

20. W1316X ___________ ___________ __________________

21. 444delA ___________ ___________ __________________

22. 3821delT ___________ ___________ __________________

23. R334W ___________ ___________ __________________

24. S549I ___________ ___________ __________________

25. G458V ___________ ___________ __________________

26. G1349D ___________ ___________ __________________

27. W846X ___________ ___________ __________________

28. 1717-1G->T __________ ___________ __________________

29. N1303K ___________ ___________ __________________

30. Y563N ___________ ___________ __________________

31. Y913C ___________ ___________ __________________

32. R553Q ___________ ___________ __________________

33. S549R(A->C)__________ ___________ __________________

34. P547H ___________ ___________ __________________

35. 1154insTC ___________ ___________ __________________

36. 1214delT ___________ ___________ __________________

37. 3659delC ___________ ___________ __________________

38. 556delA ___________ ___________ __________________

39. 621+1G->T ___________ ___________ __________________

40. E1371X ___________ ___________ __________________

41. G85E ___________ ___________ __________________

42. 711+1G->T ___________ ___________ __________________

43. G179R ___________ ___________ __________________