NEWSLETTER #56, July 23, 1993


1. Summary of CF mutations:

Name           Nucleotide      Exon       Consequence         CFTR    Reference                  
               change                                         domain                             
182delT        deletion of T   1          frameshift                  S. Shackleton, A. Harris   
               at 182                                                 (June 7)                   
F87L           T->C at 391     3          Phe->Leu at 87      TM1     T. Bienvenu, S.            
                                                                      Bousquet, N. Morral, N.    
                                                                      Fonknechten, J.C.          
                                                                      Kaplan, C. Beldjord        
                                                                      (June 7)                   
W496X          G->A at 1619    10         Trp->Stop at 496    NBF1    A. Balassopoulou (June     
W361R          T->C at 1213    7          Trp->Arg at 361             T. Bienvenu, S.            
                                                                      Bousquet, C. Herbulot,     
                                                                      N. Aiach, J.C. Kaplan,     
                                                                      C. Beldjord (June 22)      
R31C           C->T at 223     2          Arg->Cys at 31              B. Costes, N. Ghanem, M.   
                                                                      Goossens (June 25)         
3120G->A       G->A at 3120    16         splice mutation?    TM9     J. Zielenski, D.           
                                                                      Markiewicz, L.-C. Tsui     
                                                                      (June 25)                  
4040delA       deletion of A   21         frameshift          NBF2    I. Greil, K. Wagner, W.    
               at 4040                                                Rosenkranz (June 28)       
Q2X            C->T at 136     1          Gln->Stop at                L. Kalaydjieva, A.         
(together                                 codon 2                     Savov, C. Ferec, I         
with R3W?)                                                            Quere, C. Verlingue, B.    
                                                                      Mercier (June 29)          
R3W            A->T at 139     1          Arg->Trp at codon           L. Kalaydjieva et al.      
(together                                 3                           (as above)                 
with Q2X?)                                                                                       
905delG        deletion of G   6b         frameshift                  C. Ferec, I Quere, C.      
               at 905                                                 Verlingue, O. Raquenes,    
                                                                      H. Guillermit, B.          
                                                                      Mercier (June 29)          
R347C          C->T at 1171    7          Arg->Cys at 347     TM6     C. Ferec et al. (as        
R258G          G->A at 904     6b         Arg->Gly at 358             C. Ferec et al. (as        
A800G          C->G at 2531    13         Ala->Gly at 800     R       C. Ferec et al. (as        
175delC        deletion of C   1          frameshift                  C. Ferec et al. (as        
               at 175                                                 above)                     
G314R          G->C at 1072    7          Gly->Arg at 314     TM5     S. Nasr, T. Strong, L.     
                                                                      Smit, F. Collins (July 1)  
3041delG       deletion of G   16         frameshift                  S. Shackleton, A. Harris   
               at 3041                                                (July 7)                   
K14X           A->T at 172     1          Lys->Stop at 14             C. Ferec, C. Verlingue,    
                                                                      I. Quere, O. Raguenes,     
                                                                      M.P, Audrezet, H.          
                                                                      Guillermit, B. Mercier     
                                                                      (July 8)                   
D1377H         G->C at 4261    22         Asp->His at 1377    NBF2    B. Coates, N. Ghanem, M.   
                                                                      Goossens (July 8)          
3195del6       deletion of     17a        deletion of         TM10    M. Claustres, M.           
               AGTGAT from                Val1022 and                 Laussel, M. Desgeorges,    
               3195 to 3200               Ile1023                     G. Razakatzara (July 12)   
1215delG       deletion of G   7          frameshift                  M. Claustres et al. (as    
               at 1215                                                above)                     
3271+18C->T    C->T at         intron     splice mutation?            M. Claustres et al. (as    
               3271+18         17a                                    above)                     
2423delG       deletion of G   13         frameshift          R       M. Claustres, M.           
               at 2423                                                Laussel, M. Desgeorges,    
                                                                      G. Razakatzara (July 16)   
W79R           T->C at 367     3          Trp->Arg at 79              M. Macek, A. Hamosh,       
                                                                      C.L. Davis, M. Anvret,     
                                                                      G.R. Cutting July 19)      
3120+1G->A     G->A at 3120+1  intron 16  splice mutation     TM9     M. Macek et al. (as        

2. DNA sequence polymorphisms/variations in the coding region

Nucleotide position   Amino acid change          Exon    Reference                  
3032 (T or C)         Leu or Ser at 967          15      M. Claustres (July 1)      

3. Consortium report

It was suggested by many members a while ago that the Consortium should publish a summary of the observed frequencies of different CF mutations around the world. It is obviously difficult to show data for all 300 mutations but, as a compromise, I think we can squeeze [[Delta]]F508 and the next most frequent 20 or so mutations in one single table. Since the last time we collected screening data was over a year ago, there has to be some changes since then. To obtain the up to date information, I would like to ask each member to submit the data again. Although we would list only the top 20 or so mutations, we need to collect data for the top 30 mutations. In addition, it may also be useful to include a second table in the report listing some of the mutations that are frequent in subpopulations. As an arbitruary cut-off, please list those mutations that occur more than 5% of the total in your population.

If not all mutations were screened in the entire study population, it is reasonable to list the closest number (usually that done for [[Delta]]F508) as a rough estimate. Please leave a blank if the specific mutation was not tested.

The proposed title for the final report is "Population variation of cystic fibrosis mutations". The "author" of the report will be "The Cystic Fibrosis Genetic Analysis Consoritum". Names of contributors from individual laboratories will be listed in the table. A sample report is attached; the bulk of the data is derived from the last report distributed on June 4, 1992.

Please send in your data, revised numbers and corrections before July 15, 1993.

In order to save space, we would like to limit the number of authors from each data set to three and the name of affiliated institute to one (that belong to the first author). If any of the data are cited from published reports, please include the reference(s) in a foot note.

4. General Meeting

There are two possibility of having this year's General Meeting:

a) The American Society of Human Genetics Meeting in New Orleans (Oct 6-9) or

b) The North American CF Conference in Dallas (Oct 13-16); or

c) The current format is fine; no meeting necessary.

I would welcome any helpful suggestions.

Best wishes,