CF Genetic Analysis Consortium NEWSLETTER #67- January 5, 1996                        

HAPPY NEW YEAR!

1. The total number of mutations reported is 583, DNA sequence polymorphisms in the coding region is 63, and, non-coding region, 53 (see the entire lists in the attached tables). Summary of the newly reported CF mutations and DNA sequence polymorphisms:

Name of        Nucleotide      Exon    Consequence         Institute          Names of           
mutation       change                                                         Contributors       
A1364V         C->T at 4223    22      Ala->Val at 1364    Institut de        Claustres M,       
                                       CBAVD               Biologie           Carles S,          
                                                           Montpellier        Desgeorges M       
                                                                              (Jul 19)           
Note:  The above mutation was found by DGGE then direct sequencing of a CBAVD patient from                   
Southern France.  Contact: Pr. Mireille Claustres                                                            
W882X          G->A at 2777    14b     Trp->Stop at 882    Centre de          Férec C, Mercier   
                                                           Transfusion        B, Quere I,        
                                                           Sanguine et de     Lissens W,         
                                                           Biogénétique,      Bonduelle M,       
                                                           Brest, France      Liebaers (Jul 26)  
Note:  The above mutation was found on one CF chromosome in a patient of Belgian origin by    
DGGE screening and DNA sequencing.  Contact: Dr. Claude Férec                                 
3041-1G->A     G->A at 3041-1  intron  mRNA splicing       Royal Manchester   Malone G,          
                               15      mutation            Children's         Hawworth A,        
                                                           Hospital, England  Schwarz M (Aug 3)  
Note:  The above mutation was detected by SSCP/heteroduplex analysis and identified by        
direct DNA sequencing.  The mutation was found in a 4-year old female CF patient whose        
other mutation is [[Delta]]F508.  3041-1G->A was seen only once in 80 non-[[Delta]]F508       
chromosome screened.  Contact: Dr. Martin Schwarz                                             
711+3A->T      A->T at 711+3   intron  mRNA splicing       IRO, Spain         Casasl T, Ramos    
                               5       mutation?                              MD, Gimenez J,     
                                                                              Nunes V,           
                                                                              Estivill X (Aug    
                                                                              3)                 
G85V           G->T at 386     3       Gly->Val at 85      as above           as above           
Note:  The above 2 mutations were detected by DGGE and identified by direct sequencing.       
711+3A->T was found in a Spanish woman with PS, carrying R334W in the other chromosome, and   
with 2 brothers died of CF.  Screening in 132 CF patients was negative.  The patient with     
G85V carried G542X on the other chromosome, and presented mild phenotype with PI.  Contact:   
Dr. Teresa Casals                                                                             
D993Y          G->T at 3109    16      Asp->Tyr at 993     Institut de        Claustres M,       
                                                           Biologie           Desgeorges M,      
                                                           Montpellier        Carles S (Aug 4)   
Note:  The above mutation was found by DGGE and then direct sequencing of DNA from a          
patient with severe phenotype from Southern France.  Contact: Pr. Mireille Claustres          
1283delA       deletion of A   8       frameshift          Groupe             Bienvenu T,        
               at 1283                                     Hospitalier        Bousquet S,        
                                                           Cochin, Paris      Beldjord C,        
                                                                              Kaplan JC (Aug 7)  
Note:  The above mutation was detected by DGGE using chemical clamps and identified by        
direct sequencing.  It is not found in 100 other non-[[Delta]]F508 CF chromosomes and 100     
non-CF chromosomes tested.  The patient has [[Delta]]F508 on the other chromosome, a          
pancreatic deficiency and lung disease.  Contact: Thierry Bienvenu                            
Q98X           C->T at 424     4       Gln->Stop at 98     Royal Manchester   Urion A, Malone    
                                       (Pakistani          Children's         G, Hawworth A,     
                                       specific?)          Hospital, England  Schwarz M (Aug     
                                                                              14)                
Note:  The above mutation was detected by SSCP/heteroduplex analysis and identified by                       
direct DNA sequencing.  The mutation was found in homozygous form in 3 apparently unrelated                  
Pakinstani CF patients.  Q98X was seen 3 times (although in homozygous form) among 20                        
Pakistani CF chromosomes.  The first of these was from the North-West and the other 2 were                   
referred by the West Midlands Regional Genetics Service at Birmingham.  Contact: Dr. Martin                  
Schwarz.                                                                                                     
3154delG       deletion of G   17a     frameshift          Groupe             Bienvenu T,        
               at 3154                                     Hospitalier        Bousquet S,        
                                                           Cochin, Paris      Herbulot C,        
                                                                              Beldjord C,        
                                                                              Kaplan JC (Aug     
                                                                              14)                
Note:  The above mutation was detected by DGGE using chemical clamps and identified by                       
direct sequencing.  It is not found in 100 other non-[[Delta]]F508 CF chromosomes and 100                    
non-CF chromosomes tested.  The patient has R553X on the other chromosome, a pancreatic                      
deficiency and moderate lung disease.  Contact: Thierry Bienvenu                                             
Y563C          A->G at 1821    12      Tyr->Cys at 563     Princess           Delhaize C (Aug    
                                                           Margaret           22)                
                                                           Hospital for                          
                                                           Children                              
The above mutation was detected by SSCP and identified by direct sequencing.  The mutation                   
destroys an AccI site which was used for confirmation.  Contact:  Dr. E. Edkins                              
3272-9A->T     A->T at 3272-8  17a     mRNA splicing       Laboratoire de     Chomel J-C,        
                                       mutation?           Génétique          Baudis M, Kitzis   
                                                           Cellulaire et      A (Aug 23)         
                                                           Moléculaire,                          
                                                           Poitiers, France                      
Note:  The above mutation was detected by DGGE using chemical clamp and characterized by                     
direct sequencing.  Possible consequence on RNA splicing has to be examined.  Contact:                       
Jean-Claude Chomel                                                                                           
Y304X          C->G at 1044    7       Tyr->Stop at 304    Centre de          Férec C, Mercier   
                                                           Transfusion        B, Quere I (Aug    
                                                           Sanguine et de     29)                
                                                           Biogénétique,                         
                                                           Brest, France                         
Note:  The above mutation was found on a CF chromosome in a patient of French origin by                      
DGGE and DNA sequencing.  It was also found in the same family by V. Dumur and G.                            
Lalau-Lille. Contact: C. Férec                                                                               
297-2A->G      A->G at 297-2   intron  mRNA splicing       Royal Manchester   Schwarz M,         
                               2       mutation            Children's         Hawworth A,        
                                                           Hospital, England  Malone G (Sep 4)   
1717-2A->G     A->G at 1717-2  intron  mRNA splicing       as above           Hawworth A,        
                               10      mutation                               Schwarz M,         
                                                                              Malone G (Sep 4)   
Note:  The above 2 mutations were detected by SSCP/heteroduplex analysis and identified by                   
direct DNA sequencing.  297-2A->G was found in a male CF patient (referred by Dr. J. Harvey                  
of Salisbury, England) whose other mutation is [[Delta]]F508.  1717-2A->G was found in a                     
male CF patient of Romanian origin (referred by Prof. I. Popa of Timisoara, Romania) whose                   
other mutation is [[Delta]]F508.  297-2A->G and 1717-2A->G were each seen only once in over                  
100 non-[[Delta]]F508 CF chromosomes screened.  Contact: Dr. Martin Schwarz.                                 
-33G->A        G->A at -33     5'upst  promoter mutation?  Institut de        Claustres M,       
                               ream                        Biologie           Carles S,          
                                                           Montpellier        Desgeorges M       
                                                                              (Sep 8)            
Note:  The above mutation was found by DGGE and then direct sequencing of the DNA from a                     
patient with CBAVD from Southern France.  This change was not seen in any of the normal                      
alleles in the study.  Contact: Mireille Claustres                                                           
Q1144X         C->T at 3562    18      Gln->Stop at 1144   Royal Manchester   Schwarz M,         
                                                           Children's         Hawworth A,        
                                                           Hospital, England  Malone G (Sep 4)   
Nore:  The above mutation was detected by DGGE analysis and identified by direct DNA                         
sequencing.  The mutation was found on the same chromosome carrying R75Q, in a male CF                       
patient whose other mutation is [[Delta]]F508.  Q1144X was seen only once in over 150                        
non-[[Delta]]F508 chromosomes screened.  The DGGE primers were supplied by Prof. Michel                      
Goossens on behalf of the European Community Concerned Action for the Co-ordination of                       
Cystic Fibrosis Research and Therapy.  Contact: Dr. Martin Schwarz.                                          
1161insG       insertion of    7       frameshift          Virchow-Klinikum,  Varon R, Reis A    
               G after 1161                                Berlin             (Sep 21)           
Note:  The above mutation was identified by SSCP followed by direct sequencing in a German                   
CF patient with [[Delta]]F508 on the other chromosome.  The mutation was not found on 47                     
other non-[[Delta]]F508 CF chromosomes.  Contact: Dr. med. André Reis                                        
3121-1G->A     G->A at 3121-1  intron  mRNA splicing       Hôpital            Feldmann D,        
                               16      mutation            D'Enfants          Fontaine J-L,      
                                                           Armand-Trousseau   Magnier C,         
                                                                              Chauve C,          
                                                                              Plouvier E,        
                                                                              Aymard P (Sep 22)  
Note:  The above mutation was detected by DGGE and direct sequencing.  It was found in a                     
Jewish family in France.  The patient is pancreatic inssufficient, with the other CF allele                  
being W1282X.  Contact: Delphine Feldmann.  3121-1G->A was also found in a fetus at 14                       
weeks of gestation by Dr. Claude Férec (Oct 10); the fetus was said to be affected with the                  
other mutation being [[Delta]]F508.                                                                          
1243ins6       insertion of    7       insertion of Asp    Institute of       Shackleton S,      
               ACAAAA after            and Lys after       Molecular          McDowell T,        
               1243                    Lys370              Medicine, Oxford   Harris A (Oct 4)   
Note:  The above mutation was detected by SSCP analysis of exon 7.  Contact:  Ann Harris                     
V562I          G->A at 1816    12      Val->Ile at 562     Hôpital            Feldmann D,        
                                       (also reported as   D'Enfants          Balloul H,         
                                       a polymorphism by   Armand-Trousseau   Magnier C,         
                                       Fanen et al. 1992)                     Chauve C,          
                                                                              Plouvier E,        
                                                                              Aymard P (Oct 4)   
4375-15C/T     C or T at       intron  polymorphism        as above           as above           
               4375-15         23                                                                
Note:  V562I was detected by DGGE and direct sequencing.  The patient was born in Morocco                    
and is homozygous for the mutation and reported to have severe CF with pancreatic                            
insufficiency. Contact:  Dr. Delphine Feldmann.                                                              
L320V          T->G at 1090    7       Leu->Val at 320     Groupe             Bienvenu T,        
                                       CAVD                Hospitalier        Bousquet S,        
                                                           Cochin, Paris      Herbulot C,        
                                                                              Beldjord C,        
                                                                              Kaplan JC (Oct 6)  
Note:  The above mutation was detected by DGGE using chemical clamps and identified by                       
direct sequencing.  It is not found in 100 other non-[[Delta]]F508 CF chromosomes and 100                    
non-CF chromosomes tested.  The patient is presented with congenital absence of vas                          
deferece and has [[Delta]]F508 on the other chromosome.  Contact: Thierry Bienvenu                           
657delA        deletion of A   5       frameshift          Royal Manchester   Malone G,          
               at 657                                      Children's         Hawworth A,        
                                                           Hospital, England  Schwarz M (Oct     
                                                                              11)                
Nore:  The above mutation was detected by DGGE analysis and identified by direct DNA                         
sequencing.  The mutation was found on the same chromosome carrying 406-6T->C, in a male CF                  
patient whose other mutation is 1154insTC.  657delA was seen only once in over 200                           
non-[[Delta]]F508 chromosomes screened.  The DGGE primers were supplied by Prof. Michel                      
Goossens on behalf of the European Community Concerned Action for the Co-ordination of                       
Cystic Fibrosis Research and Therapy.  Contact: Dr. Martin Schwarz.                                          
E822X          C->T at 2596    13      Glu->Stop at 822    Athens             Tzetis M,          
                                                           University,        Antoniadi T,       
                                                           Greece             Kanavakis E (Oct   
                                                                              11)                
Note:  The above mutation was detected by DGGE and confirmed by direct sequencing.  It was                   
found in 4 of 572 CF chromosomes screened (0.84%).  The genotypes of the 4 Greek patients                    
are:  [[Delta]]F508/E822X, 3272-26A->G/E822X, 621+1G->T/E822X and E822X/?.  Contact:  Dr.                    
med. E. Kanavakis                                                                                            
CF40kbdel(?)   deletion of     4-10    large deletion      Yorkshire          Logan WP, Taylor   
               exons 4-10              from intron 3 to    Regional           GR (Oct 16)        
                                       intron 10           Laboratory                            
Note:  The above mutation was detected as a null PCR product for exons 4, 7, IVS8(CA)n and                   
exon 10 in a consangineous Pakistani pedigree.  Positive PCR products were detected for                      
exons 3, 11 and IVS17b(TA)n.  The limits of the deletion have not yet been defined.  It may                  
be the same as that described by Chevalier-Porst & Bozon in NL#66.  The mutation name                        
assignment is therefore provisional.  Contact:  Dr. G.R. Taylor                                              
3153delT       deletion of T   17a     frameshift          Laikon General     Balassopoulou A,   
               at 3152 or                                  Hospital, Greece   Hatzipangiotou N   
               3153                                                           (Nov 2)            
                                                           Athens             Tzetis M,          
                                                           University,        Antoniadi T,       
                                                           Greece             Kanavakis E (Dec   
                                                                              14)                
Note:  The above mutation was identified by DGGE and direct sequencing on the paternal CF                    
chromosome of a patient whose other chromosome carries N1303K.  It was found once among the                  
80 CF chromosomes screened for mutations in exon 17a.  Contact: Dr. Angeliki Balassopoulou.                  
This mutation was also independently reported by Tzetis et al. as 3152delT, in a 3-year old                  
patient with PI, sweat Cl of 92.2mEq/L and moderate lung disease; the associated haplotype                   
is 16-31-27 (IVS8CA-17BTA-17BCA); [[Delta]]F508 was found on the other chromosome with                       
haplotype of 17-31-13.  Contact:  Dr. Emmanuel Kanavakis.                                                    
G576X          G->T at 1858    12      Gly->Stop at 576    Hôpital Henri      Girodon E,         
                                                           Mondor, Creteil,   Costes B,          
                                                           France             Cazeneuve C,       
                                                                              Ghanem N,          
                                                                              Goossens M (Nov    
                                                                              10)                
M952I          G->C at 2988    15      Met->Ile at 952     as above           as above           
                                       CBAVD mutation?                                           
Note:  The above 2 mutations were discovered by DGGE and identified by direct sequencing.                    
G576X was found in a 4-year old Romanian patient who has severe pulmonary infection since                    
the age of 18 months; the other mutation for this patient is unknown.  M952I was found in a                  
CBAVD patient who also carries R117H but it was unclear if the 2 mutations were located on                   
different chromosomes due to the lack of family members.  Other CFTR gene regions also                       
remain to be examined.  The mutation status of M952I is thus tentative.  Contact:  Prof.                     
Michel Goossens.                                                                                             
E826K          G->A at 2608    13      Glu->Lys at 826     Institute of       Bombieri C,        
                                                           Biology and        Benetazzo MG,      
                                                           Genetics,          Saccomani A,       
                                                           Verona, Italy      Pignatti PF (Dec   
                                                                              5)                 
Note:  The above sequence alteration was found by DGGE analysis of a sarcoidosis patient.                    
It was sequenced and confirmed with a Restriction site Generating PCR assay.  It was absent                  
by DGGE analysis in 208 control chromosomes, and by sequencing 60 chromosomes with unknown                   
CFTR mutations. Contact:  Dr. Cristina Bombieri.                                                             
[[Delta]]L453  deletion of 3   9       deletion of Leu     Medizinische       Dörk T, Skawran    
               bp between              at 452 or 454       Hochschule         B, Antonin W,      
               1488 and 1494                               Hannover, Germany  Ebhard M, Stegh    
                                                                              A, Ellemunter H,   
                                                                              Schmidtke J,       
                                                                              Stuhrmann M (Dec   
                                                                              7)                 
Y577F          A->T at 1862    12      Tyr->Phe at 577     as above           as above           
1874insT       insertion of    12      frameshift          as above           as above           
               T between                                                                         
               1871 and 1874                                                                     
3425delG       deletion of G   17b     frameshift          as above           as above           
               at 3425 or                                                                        
               3426                                                                              
492G/A         G->A at 492     4       polymorphism        as above           as above           
                                       (Ala120 no change)                                        
Note:  [[Delta]]L453 (or 454) was identified in an Austrian CF family from Tyrol.  The male                  
patient had severe CF and carrier [[Delta]]L453 on his maternal and [[Delta]]F508 on the                     
paternal allele.  Mutation Y577F and 1874insT were found together in another CF patient                      
from Austria; this boy is also heterozygous for [[Delta]]F508.  3425delG was identified in                   
a German CF family from lower Saxonia; the affected girl crried 3425delG on her paternal                     
and [[Delta]]F508 on the maternal allele.  The sequence variant 492G/A was seen once in a                    
CBAVD patient with yet unknown CFTR mutations.  Contact: Dr. med. Manfred                                    
Stuhrmann-Spangenberg.                                                                                       
L1065R         T->G at 3326    17b     Leu->Arg at 1065    Institut de        Casals T, Ramos    
                                                           Recerca            MD, Gimenez J,     
                                                           Oncologica, Spain  Nunes V,           
                                                                              Estivill X (Dec    
                                                                              12)                
2790-108G/C    G->C at         intron  polymorphism        as above           Casals T, Ramos    
               2790-108        14b                                            MD, Gimenez J,     
                                                                              Nunes V, Bal J,    
                                                                              Mazurczak T,       
                                                                              Estivill X (Dec    
                                                                              12)                
Note:  L1065R was observed by direct sequencing after detection of an abnormal DGGE                          
pattern.  The CF patient is a 6-year old girl with PI, carrying [[Delta]]F508 mutation in                    
the other chromosome.  The G->C polymorphism at 2790-108 was similarly detected in a Polish                  
CF patient.  Contact: Teresa Casals                                                                          
156G/A         G->A at 156     exon 1  polymorphism        Institut de        Claustres M,       
                                       (Lys8 no change)    Biologie           Romey M-C,         
                                                           Montpellier        Desgeorges M       
                                                                              (Dec 13)           
Note:  The above polymorphism which destroys a HaeIII restriction site was detected by DGGE                  
and direct sequencing of the normal chromosome of the mother of a CF patient from Lebanon.                   
This change was not found in the normal alleles from Southern France.  Contact:  Pr.                         
Mireille Claustres.                                                                                          
3041-52C/G     C->G at         intron  polymorphism        Athens             Tzetis M,          
               3041-52         15                          University,        Antoniadi T,       
                                                           Greece             Kanavakis E (Dec   
                                                                              14)                
Note:  The above sequence alteration was found once among 500 CF chromosomes screened.                       
Contact:  Dr. Emmanuel Kanavakis.                                                                            
G392A          T->C at 1307    8       Gly->Ala at 392     Groupe             Bienvenu T,        
                                       CAVD                Hospitalier        Bousquet S,        
                                                           Cochin, Paris      Herbulot C,        
                                                                              Beldjord C,        
                                                                              Kaplan JC (Dec     
                                                                              15)                
1296G/T        G->T at 1296    8       polymorphism        as above           as above           
                                       (Thr388 no change)                                        
T1086I         C->T at 3389    17b     Thr->Ile at 1086    as above           as above           
Note:  The above 3 sequence alterations were detected by DGGE using chemical clamps and                      
identified by direct sequencing.  G392A was found in a patient presented with congenital                     
absence of vas deferece and [[Delta]]F508 on his other chromosome; it was not found in 100                   
other non-[[Delta]]F508 CF chromosomes and 100 non-CF chromosomes tested.  The G->T                          
polymorphism was detected in a non-CF subject.  T1086I was found in a 34-year old, CF adult                  
female patient with PI, moderate pulmonary disease and sweat Cl of 113 mEq/L and unknown                     
CFTR mutation on her other chromosome; it was not found in 200 other non-[[Delta]]F508 CF                    
chromosomes and 200 non-CF chromosomes tested.  Contact: Thierry Bienvenu                                    
132C->G        C->G at 132     1       altered             Institut de        Claustres M,       
                                       transcription       Biologie           Desgeorges M,      
                                       rate?               Montpellier        Romey M-C (Dec     
                                                                              22)                
T582I          C->T at 1877    12      Thr->Ile at 582     as above           as above           
15G/A          G->A at 15      1       polymorphism?       as above           as above           
Note:  The C->G change at 132 destroys an NlaIII restriction site.  Contact: Pr. Mireille                    
Claustres.                                                                                                   
L127X          T->G at 512     4       Leu->Stop at 127    Centre de          Férec C,           
                                                           Transfusion        Verlingue C.       
                                                           Sanguine et de     Mercier B,         
                                                           Biogénétique,      Quéré, I (Dec 27)  
                                                           Brest, France                         
Note:  The above mutation was found once by DGGE and DNA sequencing.  Contact: Dr. Claude                    
Férec.                                                                                                       

2. D. Hughes, A. Hill, and C. Graham (Oct 3) noted with apology that the previously reported mutation S10R did not exist; it was a sequencing artifact corresponding to a G to C change of the 129G/C polymorphism associated with R117H.

3. There were a number of reports on "novel" mutations which had been discribed earlier as polymorphisms. Except for V562I, the others were not printed in the above table as there was no good evidence for disease-causing. Consortium members please check the polymorphism summary tables as well when reporting mutations.

4. Dr. Dieter Gruenert of University of California at San Francisco has sequenced almost 3 kb of intron 9 just upstream of exon 10. He has indicated a willingness to share his sequence with Consortium members. More important, a number of errors in the sequence published by J. Zielenski et al. in their 1991 Genomics paper has been noted by Gruenert and Zielenski, as shown below:

746 790

GUENERT: CAACTGTTAGCTGTTACTAACCTTTCCCATTCTTCCTCCAAACC

GENOMICS: C ACTG TAGCTG TACT ACC TT CCA TC TCCT C AACC

1525-307 1525-274

811 820

GUENERT: TGTGCCCCTT

GENOMICS: TGTGCCC TT

1525-253 1525-245

1541 1550

GUENERT: AAACGTCCTC

GENOMICS: AAACGTC TC

1716+285 1716+295

1571 1580

GUENERT: GCATATAAGT

GENOMICS: GCATATA GT

1716+315 1716+323

Since the above segments were towards the end of the published sequence, consortium members might have not been able to design PCR primers from that region of the intron. Zielenski et al. wish to send their apology.

Please contact Dr. Gruenert for the entire unpublished sequence: 203 Surge, Box 0911, Cardiovascular Research Institute, Gene Therapy Core Center, School of Medicine, University of California, San Francisco, CA 94143-0911, USA. Telephone: (415) 476-7934; Fax: (415) 476-9749; e-mail: <gruenert@labmed.uscf.edu>

5. You can access the CF Mutation Database via the World Wide Web; the address is <http://genet.sickkids.on.ca/cftr/>. As we discussed at the last Consortium meeting at the American Society of Human Genetics meeting in Minneapolis, the database is now widely accessible by the public. The information should therefore be updated as much as possible. Please let me know of any inaccuracy in the summary tables and any revised references. I have also been able to send the Newsletter out by e-mail to about 20 members of the Consortium, saving me about $100 of postage. Half of these members responded the next day saying that everything was properly received but some members had trouble reading the attached files. Since the tables were generated by a Macintosh computer, even though with an interchangeable format, it may be problematic for IBM PC users. ASCI files will loose the format. But, I will find a way to solve the problem. Please send me your e-mail address so that we can save more money in the future. A list of consortium members will be posted shortly.

6. Please drop me note by e-mail if you have seen the www page and give me any suggestions regarding future improvements. My new address is <lctsui@genet.sickkids.on.ca> although the old one should still work.

Regards,

Contacts:

Dr. Angeliki Balassopoulou; Address: Center if Thalassemias, Unit of Prenatal Diagnosis, 16 Sevastoupoleos Street, Ampelokipi 11526, Athens, Greece; Telephone: +30 1-77.89.476 ; FAX: +30 1-77.57.442

Dr. Thierry Bienvenu, Laboratoire de Biochemie Génétique, Groupe Hospitalier Cochin, 27, rue du fg Saint-Jacques, 75679 Paris Cedex 14, France. Telephone: +33 (1) 42 34 12 12; FAX: +33 (1) 44 41 15 22

Dr. Cristina Bombieri; Address: Istituto di Biologia e Genetica, Università di Verona, Strada Le Grazie 8, 37134 Verona, Italy; Telephone: +39 45 8098183; FAX: +39 45 8098180; e-mail: cristy@borgoroma.univr.it

Dr. Dominique Bozon; Address: Biochimie Bât D, Hôpital Debrousse, 29 rue Soeur Bouvier, 69322 Lyon, Cedex 05, France; Telephone: +33 72.38.57.21; FAX: +33 72. 38.58.84

Dr. Jean-Claude Chomel; Address: Centre Hospitalier Universitaire de Poitiers, Hôpital Jean-Benard- La Milétrie- BP 577-86021, Pointiers Cedex; Telephone: +33 49.44.39.03 /57.94 /57.95; FAX: +33 49.44.39.12

Pr. Mireille Claustres; Address: Laboratoire de Biochimie Génétique, Institut de Biologie, Boulevard Henri IV, 34060 Monpellier Cedex, France; Telephone: +33 67 60 11 81; FAX: +33 67 60 95 06; E-mail:

Dr. Harry Cuppens; Address: Center for Human Genetics, University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium Telephone: +32 16-34.58.60; FAX: +32 16-34.59.97; E-Mail: Harry=Cuppens%COM%CME@cc3.kuleuven.ac.be

Dr. Garry R. Cutting; Address: Center for Medical Genetics, 600 N. Wolfe Street, CMSC 1004, Baltimore, MD 21287-3914; Telephone: +1 (410) 614-0211; FAX: +1 (410) 955-0484; e-mail: mmacek@welchlink.welch.jhu.edu

Dr. Ângela Duarte; Address: Departmento de Genética Humana, Instituto Nacional de Saúde, Av. Padre Cruz, 1699 Lisboe Codex, Portugal; Telephone: 351.1.7585129; FAX: 351.1.7590441

Dr. Ted Edkins, Clinical Chemistry, Princess Margaret Hospital for Children, Australia; Telephone: +61 9 340 8595; FAX: +61 9 340 8117; e-mail: margchld@angis.su.oz.au

Dr. Delphine Feldmann; Address: Laboratoire de Biochimie, Hôpital D'Enfants Armand-Trousseau, 26 avenue du Dr Arnold-Netter, 75571 Paris Cédex 12, France; Telephone: +33 44.73.68.67; FAX: +33 44.73.66.87

Dr. Claude Férec; Address: Centre de Biogénétique, Centre de Transfusion Sanguine et de Biogénétique, 46 Rue Félix Le Dantec - B.P. 454 - 29275 BREST Cédex, France; Telephone: +33 98.44.50.64; FAX: +33 98.43.05.55; e-mail: Claude.Ferec@univ-brest.fr

Pr. Damjan Glavac; Address: National Institute of Chemistry, SI-61115 Ljubljana, Hajdrihova 19, Slovenia, P.O.B. 30; Telephone: (+386 61) 123-20-61; FAX: (+386 61) 125-92-44/125-70-69

Prof. Michel Goossens; Address: INSERM U.91, CHU Henri Mondor, 51 Av. du Maréchal de Lattre de Tassigny, 94010 CRETEIL, France; Telephone: +33 (1) 49 81 28 60; FAX: +33 (1) 49 81 28 42

Laurent Gouya; Address: Laboratoire de Biochemie Génétique, Hôpitaux Robert Debré, 48, Bd Sérurier, 75019 Paris; Telephone: + 33 (1) 40.03.20.00; FAX: (1) 40.03.20.20

Dr. Ann Harris, Institute of Molecular Medicine, Oxford; e-mail: aharris@molbiol.ox.ac.uk

Dr. David Hughes; Address: Department of Medical Genetics, Floor A, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB Telephone: (0232) 329241; FAX: (0232) 236911

P Jézéquel/Y.E. le Gall; Address: Départment de Biochimie et Biologie Molecularie, Universite de Rennes I, 2 Avenue du Professeur Léon Bernard, 35043 Rennes Cédex, France; Telephone: 33.99.33.68.20; FAX: 33.99.33.68.98; E-Mail: legall@univ-rennes1.fr

Dr. med. Emmanuel Kanavakis; Address: Anthens University, First Dept. of Pediatrics, Unit of Molecular Medicine, St. Sophia Children's Hospital, Athens 11527, Greece; Telephone/FAX: (031) 7795762; E-Mail: ekanavak@atlas.uoa.ariadne-t.gr

Dr. Jean Claude Kaplan; Address: Laboratoire de Biochemie Génétique, Groupe Hospitalier Cochin, 27 rue de fg Saint-Jacques, 75679 Paris Cedex 14; Telephone: +33 (1) 42.34.12.12; FAX: +33 (1) 44.41.15.22

Prof.dr. Radovan Komel ; Address: Institute of Biochemistry, Medical Faculty, Vrazov trg2, 61000 Ljubljana, Slovenia; Telephone: (+386 61) 312 357; FAX: (+386 61) 132 0016

Prof. Inge Liebaers; Address: Center for Medical Genetics, Free University Hospital Brussels, Laarbeeklaan 101, 1090 Brussels, Belgium; Telephone: +32 (02) 477.60.71; FAX: +32 (02) 477.58.00

Dr. Virginia Nunes / Teresa Casals; Address: Institut de Recerca Oncologica, Hospital Duran i Reynols, Autovia de Castelldefels km. 2.7, Hospitalet, 08907 Barcelona, Catalunya, Spain; Telephone: (34-3) 335 71 52; FAX: (34-3) 263 22 51; E-Mail: vnunes@gm.iro.es

Dr. med. André Reis; Adress: Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin; Telephone: +49 (030) 450 66113; FAX (030) 450 66904; e-mail reis@ukrv.de

Dr. Martin Schwarz; Address: Regional Molecular Genetics Laboratory, Royal Manchester Children's Hospital, Hospital Road, Pendlebury, Manchester M27 4HA; Telephone: 0161-794 4696; FAX: 0617272328

Dr. med. Manfred Stuhrmann-Spangenberg; Address: Institut für Humangenetik OE 6300, Zentrum Kinderheilkunde und Humangenetik, Medizinische Hoschule Hannover, D- 30625 Hannover, Germany; Telephone: +49 (511) 532-3719; FAX: +49 (511) 532-5865

Dr. G.R. Taylor, Yorkshire REgional DNA Laboratory, Clinical Genetics Unit, Ashley Wing, St. Jame's University Hospital, Leeds LS9 7TF; Telephone +44 (0113) 283 7083; FAX: (0113) 246 7090; e-mail: gtaylor@hgmp.mrc.ac.uk

Dr. Lap-Chee Tsui; Address: Department of Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8 CANADA; Telephone: +1 (416) 813 6015 FAX: +1 (416) 813 4931; E-Mail: lctsui@genet.sickkids.on.ca

Andrew Wallace; Address: Regional Molecular Genetics Laboratory, Department of Medical Genetics, St. Mary's Hospital, Hathersage Road, Manchester M13 0JH; Telephone: 061-276-6129/6122; FAX: 061-274-3159

Dr. Julian Zielenski; Address: Department of Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8 CANADA; Telephone: +1 (416) 813 6365 ; FAX: +1 (416) 813 4931; E-Mail: julian@genet.sickkids.on.ca