CFTR mutations in Turkish and North African cystic fibrosis patients in Europe: implications for screening.
OBJECTIVE
To obtain more insight into the variability of the CFTR mutations found in immigrant cystic fibrosis (CF) patients who are living in Europe now, and to estimate the test sensitivity of different frequently used methods of DNA analysis to detect CF carriers or patients among these Turkish or North African immigrants.


METHODS
A survey among 373 European CF centers asking which CFTR mutations had been found in Turkish and North African CF patients.


RESULTS
31 and 26 different mutations were reported in Turkish and North African patients, identifying 64.2% (113/176) and 87.4% (118/135) alleles, respectively (p < 0.001). The mean sensitivity (detection rate) of three most common CFTR mutation panels to detect these mutations differed between Turkish and North African people, 44.9% (79/176) versus 69.6% (94/135) (p < 0.001), and can be increased to 57.4% (101/176) and 79.3% (107/135) (p < 0.001), respectively, by expanding these panels with 13 mutations which have been found on two or more alleles.


CONCLUSIONS
35.8% and 12.6%, respectively, of CF alleles in Turkish and North African patients living in Europe now had not been identified. Among these populations, the test sensitivity of common CFTR mutation panels is insufficient for use in screening programs in Europe, even after expansion with frequent Turkish and North African mutations. This raises questions about whether and how to implement CF carrier and neonatal screening in a multiethnic society.
Lakeman
Phillis
P
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. p.lakeman@vumc.nl
Gille
Johan J P
JJ
Dankert-Roelse
Jeannette E
JE
Heijerman
Harry G M
HG
Munck
Anne
A
Iron
Albert
A
Grasemann
Hartmut
H
Schuster
Antje
A
Cornel
Martina C
MC
Ten Kate
Leo P
LP
D000293:Adolescent; D000328:Adult; D000352:Africa, Northern / Q000208:ethnology; D000483:Alleles; D002648:Child; D003241:Consanguinity; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods / Q000706:statistics & numerical data; D004641:Emigration and Immigration; D005060:Europe; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005820:Genetic Testing / Q000379:methods* / Q000706:statistics & numerical data; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D010290:Parents; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires; D014421:Turkey / Q000208:ethnology
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator