TO: MEMBERS OF THE CYSTIC FIBROSIS GENETIC ANALYSIS CONSORTIUM

Amos, Boston U, USA 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

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,TheNetherlands

Godet, Villeurbanna, France Schmidtke, IHG, Berlin

Goossens, Creteil, France Schwartz, U Copenhagen, Denmark

Graham, Belfast, N Ireland Sebastio, Naples, Italy

Gruenert, UCSF, USA Seltzer, U Colorado, USA

Halley, Rotterdam, The Netherlands Spona, Vienna, Austria

Harris, Guy's-London, England Super, Royal Manchester, England

Highsmith, NC Mem Hosp, USA Thibodeau, Rochester, USA

Horst, Münster, West Germany Tümmler, Hannova, West Germany

Jaume-Roig, Son Dureta, Spain Verellen-Dumoulin,Bruxelles,Belgium

Kalaydjieva, Sofia, Bulgaria Willems, U Antwerp, Belgium

Kant, U Penn, USA Williamson,St Mary'sLondon,England

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FROM: LAP-CHEE TSUI TOTAL NUMBER OF PAGES: 8

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NEWSLETTER #14, April 17, 1990

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Dear members,

1. Goossens and Vidaud have reported a point mutation in exon 15 (Y913C).

2. Cassiman reports an error in the description of ASO for the G458V mutation; the normal ASO should be 5'-GTT GCT GGA TCC ACT G-3' and the mutant 5'-GTT GCT GTA TCC ACT G-3' (the last G was missing in both).

3. The Consortium report on [[Delta]]F508 has been accepted for publication in Am. J. Hum. Genet. but the Editor did not agree with the way the table was organized by the number of chromosome tested. He suggested that we should list them by countries in alphabetical order, with the different groups from each country listed in the same area, one after the other. I have reshuffled the data according to the suggestion but I have not made any attempt to change the listing of locations. The revised Table 1 is attached; if there is any serious objection please let me know quickly because I need to submit the revised table by April 25 in order for the letter to be included in the August 1990 issue. I guess we should cite this work as "Worldwide Survey of the [[Delta]]F508 Mutation- Report from the Cystic Fibrosis Genetic Analysis Consortium. Am.J.Hum.Genet. (accepted)".

4. A meeting of the Consortium members was held at the recent CF Conference in Sestri Levante, Italy. The main items discussed are summarized below:

a. Membership issues- There are currently 70 members in the consortium and a few more waiting to join. There is a general feeling that, while most members are making contributions to the consortium, ie. actively hunting for additional mutations and collecting population data, some are not living up to their commitment. For this reason, there will be more stringent rules when accepting new members; each application has to be reviewed and approved by at least 3 of the 4 members of the Steering Committee. We will not accept any applicant whose sole intend (or apparent motive) is to receive information about mutation data. In addition, we should receive explanation from those members who have not yet contributed to the consortium.

b. Publication of data contributed to the consortium- Publication of mutation information is absolutely not allowed without the consent of the primary member (group) who reported the mutation. Charlie Epstein of AJHG has already agreed to print the joint report on [[Delta]]F508 screening. Victor McKusick would be happy to publish a cluster of papers or one big consortium paper on CF mutations in GENOMICS. OMIM database should only list published data; the information reported to the consortium need to be confirmed. Members should treat the reported mutations with extreme caution for diagnostic or population screening purpose, as some of them may not be true mutations. In addition, diagnosis based on the destruction of restriction sites may not recognize the exact alteration; even oligonucleotide hybridization may have unexpected results. Members should therefore use the information published in the newsletter for research purposes only. It would be self-evident when a mutation is worth-testing in the clinic.

c. Coordinating screening efforts- There are simply too many additional mutations; it is difficult for any lab to perform tests for over 20 different ones in a short period of time. On the other hand, it is difficult to provide general guidance because there is likely to be geographic variation for the frequencies of different mutations. It is generally felt that G551D, G542X and S549I might be more frequent than others. In order to facilitate data compilation, members are requested to send the results back to the original (reporting) lab as soon as possible. It is important to report negative data. For the consortium database, requests for data updates will be circulated periodically (see below).

d. A general meeting will be held at the International CF Conference (tentatively scheduled in the evening of October 4).

5. A table of all the mutations identified to date is attached; please use the table to report your data to the consortium, even if you have reported your data previously. Haplotype data are not required. Please return the table by May 1.

6. A copy of condensed Newsletter 1-13 was sent off by regular mail last week. Copies of future Newsletters will also be followed by regular mail.

Best regards,

Standardized population screening report to the consortium

(Please return by May 1, 1990)

From (Name of principal investigator): ___________________________

Patient population (Location / ethnic origin):

(use different sheets for different populations)

Number of chromosomes

Name Total CF* 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 ___________ ___________ __________________

5. I506V ___________ ___________ __________________

6. G551D ___________ ___________ __________________

7. S549N ___________ ___________ __________________

8. R553X ___________ ___________ __________________

9. A559T ___________ ___________ __________________

10. G542X ___________ ___________ __________________

11. S549R ___________ ___________ __________________

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. Q493X ___________ ___________ __________________

25. S549I ___________ ___________ __________________

26. G458V ___________ ___________ __________________

27. G1349D ___________ ___________ __________________

28. W864X ___________ ___________ __________________

29. 1717-1G->T___________ ___________ __________________

30. N1303K ___________ ___________ __________________

31. Y563N ___________ ___________ __________________

32. Y913C ___________ ___________ __________________