ABCMdb

PMID: 17481968

Storm K, Moens E, Vits L, De Vlieger H, Delaere G, D'Hollander M, Wuyts W, Biervliet M, Van Schil L, Desager K, Nothen MM
High incidence of the CFTR mutations 3272-26A-->G and L927P in Belgian cystic fibrosis patients, and identification of three new CFTR mutations (186-2A-->G, E588V, and 1671insTATCA).
J Cyst Fibros. 2007 Nov 30;6(6):371-5. Epub 2007 May 3., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Glu588Val ABCC7 p.Glu588Val High incidence of the CFTR mutations 3272-26A→G and L927P in Belgian cystic fibrosis patients, and identification of three new CFTR mutations (186-2A→G, E588V, and 1671insTATCA) Katrien Storm a,⁎, Els Moens b , Lieve Vits a , Haike De Vlieger a , Gino Delaere a , Maria D'Hollander a , Wim Wuyts a , Martine Biervliet a , Lutgardis Van Schil c , Kristine Desager b , Markus M. Nöthen a,1 a Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium b Department of Pediatrics, University Hospital of Antwerp, Antwerp, Belgium c Department of Pneumonology, Sint-Vincentiusziekenhuis, Antwerp, Belgium Accepted 10 October 2006 Available online 3 May 2007 Abstract We have analyzed 143 unrelated Belgian patients with a positive diagnosis of cystic fibrosis (CF) for mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Login to comment 3 ABCC7 p.Glu588Val ABCC7 p.Glu588Val In addition to 10 previously reported mutations we identified 2 new mutations 186-2A→G and E588V. Login to comment 5 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro Two mutations were detected with a higher frequency than expected: 3272-26A→G, which is the second most common mutation after ΔF508 in our CF population with a frequency of 3.8%, and L927P (2.4%). Login to comment 6 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Glu588Val ABCC7 p.Glu588Val The clinical data is presented for the mutations 186-2A→G, E588V, 3272-26A→G and L927P. Login to comment 31 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ser1251Asn ABCC7 p.Ser1251Asn ABCC7 p.Arg560Thr ABCC7 p.Arg560Thr ABCC7 p.Gln552* ABCC7 p.Gln552* The Inno Lipa™ CFTR12 assay contains normal and mutant probes for 12 different CFTR mutations (ΔF508, G542X, N1303K, 1717-1G→A, W1282X, G551D, R553X, S1251N, R560T, 3905insT, Q552X, ΔI507). Login to comment 32 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Glu60* ABCC7 p.Glu60* The Inno Lipa™ CFTR17 assay contains normal and mutant probes for 17 other CFTR mutations (394delTT, G85E, 621+1G→T, R117H, 1078delT, R347P, R334W, E60X, 711+5G→A, 2789 + 5G→ A, R1162X, 3659delC, 3849 + 10kbC→ T, 2143delT, A455E, 2183AA→G, 2184delA) (Innogenetics). Login to comment 54 ABCC7 p.Glu588Val ABCC7 p.Glu588Val From the 12 different mutations identified by DGGE 10 mutations are reported before and 2 mutations (186-2A→G and E588V) are new. Login to comment 60 ABCC7 p.Gly542* ABCC7 p.Ser1251Asn ABCC7 p.Leu927Pro L927P (together with G542X and S1251N) is the fourth most common CFTR mutation, with a frequency of 2.4%. Login to comment 64 ABCC7 p.Leu927Pro Also the incidence of the mutation L927P differs between different parts of Belgium and seems to be the highest for Antwerp (with frequencies from 0.3 up to 2.4%). Login to comment 76 ABCC7 p.Leu927Pro L927P. Login to comment 77 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro The mutation L927P is caused by the transition of a T to C at nucleotide position 2912 in exon 15, and changes a leucine to a proline at position 927 of the protein. Login to comment 78 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro The L927P is described before by Hermans et al. [13] in 3 families (5 patients). Login to comment 79 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro They concluded that most likely L927P can be classified as a severe CF mutation comparable with ΔF508. Login to comment 80 ABCC7 p.Ser1251Asn ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro We found L927P in 7 CF patients: four patients have ΔF508 as the second mutation, one patient 1717-1G→A, another patient S1251N, and a last patient 2789+ 5G→A. Login to comment 81 ABCC7 p.Ser1251Asn ABCC7 p.Leu927Pro We found L927P in 7 CF patients: four patients have ƊF508 as the second mutation, one patient 1717-1G࢐A, another patient S1251N, and a last patient 2789+ 5G࢐A. Login to comment 83 ABCC7 p.Ser1251Asn ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro The patients described in Table 3 presented more gastro-intestinal problems and Table 2 Frequency of the mutations 3272-26A→G and L927P for different parts of Belgium and other countries Country/Region Frequency 3272-26A→G (%) Reference Belgium/Antwerp 3.8 This study Belgium/Brussels 1.7 W. Lissens, pers. comm. Belgium/Ghent 0.9 L. Messiaen, pers. comm. Belgium/Leuven 1.0 [14] The Netherlands 0.9 H. Scheffer, pers. comm. France 0.5 [15-17] Germany 0.9 [18] Greece 0.8 [19,20] Spain 0.5 [21] Canada (Toronto) 0.5 [22] Portugal 2.0 [11] South Africa (white population) 4.2 [23] Frequency L927P (%) Belgium/Antwerp 2.4 This study Belgium/Brussels 0.7 W. Lissens, pers. comm. Belgium/Gent 0.3 L. Messiaen, pers. comm. The Netherlands 0.5 [13] Table 3 Clinical phenotypes of patients compound heterozygous for L927P and a second mutation Genotype (L927P/any) Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Second mutation ΔF508 ΔF508 ΔF508 ΔF508 1717-1GNA S1251N Sex Male Female Male Female Female Female Age at diagnosis 1 month (meconium ileus) ? Login to comment 84 ABCC7 p.Ser1251Asn ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro The patients described in Table 3 presented more gastro-intestinal problems and Table 2 Frequency of the mutations 3272-26A࢐G and L927P for different parts of Belgium and other countries Country/Region Frequency 3272-26A࢐G (%) Reference Belgium/Antwerp 3.8 This study Belgium/Brussels 1.7 W. Lissens, pers. comm. Belgium/Ghent 0.9 L. Messiaen, pers. comm. Belgium/Leuven 1.0 [14] The Netherlands 0.9 H. Scheffer, pers. comm. France 0.5 [15-17] Germany 0.9 [18] Greece 0.8 [19,20] Spain 0.5 [21] Canada (Toronto) 0.5 [22] Portugal 2.0 [11] South Africa (white population) 4.2 [23] Frequency L927P (%) Belgium/Antwerp 2.4 This study Belgium/Brussels 0.7 W. Lissens, pers. comm. Belgium/Gent 0.3 L. Messiaen, pers. comm. The Netherlands 0.5 [13] Table 3 Clinical phenotypes of patients compound heterozygous for L927P and a second mutation Genotype (L927P/any) Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Second mutation ƊF508 ƊF508 ƊF508 ƊF508 1717-1GNA S1251N Sex Male Female Male Female Female Female Age at diagnosis 1 month (meconium ileus) ? Login to comment 93 ABCC7 p.Leu927Pro Children with L927P were mostly diagnosed in the neonatal period. Login to comment 94 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro From this, we conclude that patients with L927P show clinical features comparable to patients homozygous for ΔF508. Login to comment 95 ABCC7 p.Leu927Pro From this, we conclude that patients with L927P show clinical features comparable to patients homozygous for ƊF508. Login to comment 104 ABCC7 p.Glu588Val E588V. Login to comment 105 ABCC7 p.Glu588Val ABCC7 p.Glu588Val The missense mutation E588Vis caused by a transversion of A to T at nucleotide 1895 in exon 12 of the CFTR gene leading to a change of glutamic acid to valine at amino acid position 588. Login to comment 106 ABCC7 p.Glu588Val The missense mutation E588Vis caused by a transversion of A to T at nucleotide 1895 in exon 12 of the CFTR gene leading to a change of glutamic acid to valine at amino acid position 588. Login to comment 107 ABCC7 p.Glu588Val The patient is compound heterozygous for ΔF508 and E588V. Login to comment 108 ABCC7 p.Glu588Val ABCC7 p.Glu588Val Arguments for a pathogenic character of E588V are (1) the mutation was not detected in 96 control chromosomes, (2) a relative large charged polar amino acid is substituted by a small apolar amino acid. Login to comment 109 ABCC7 p.Glu588Val Arguments for a pathogenic character of E588V are (1) the mutation was not detected in 96 control chromosomes, (2) a relative large charged polar amino acid is substituted by a small apolar amino acid. Login to comment 113 ABCC7 p.Glu588Val Twenty-five different mutations were identified including two new CFTR mutations 186-2A→G and E588V. Login to comment 114 ABCC7 p.Leu927Pro ABCC7 p.Glu588Val Two known mutations 3272-26A→G and L927P were shown to occur with a higher frequency in Antwerp compared to other Belgian regions. Login to comment 115 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro We conclude that 3272-26ANG is a milder mutation than ΔF508, as reported before by Amaral et al. [12], and that L927P can be classified as a severe mutation comparable with ΔF508. Login to comment 116 ABCC7 p.Leu927Pro ABCC7 p.Leu927Pro Acknowledgements We would like to thank Dr. Sc. W. Lissens (Department of Medical Genetics, University Hospital of the Free University of Brussels, Belgium), Dr. Sc. L. Messiaen (Department of Medical Genetics, University Hospital of Ghent, Belgium; current address: Laboratory of Medical Genomics, University of Alabama, Birmingham, USA), and Dr. Sc. H. Scheffer (Department of Medical Genetics, University of Groningen, The Netherlands; current address: Department of Human Genetics, Radboud University Nijmegen Medical Center, The Netherlands) to communicate the information on the frequencies of the mutations 3272-26A→G and L927P in their CF population. Login to comment 117 ABCC7 p.Leu927Pro Acknowledgements We would like to thank Dr. Sc. W. Lissens (Department of Medical Genetics, University Hospital of the Free University of Brussels, Belgium), Dr. Sc. L. Messiaen (Department of Medical Genetics, University Hospital of Ghent, Belgium; current address: Laboratory of Medical Genomics, University of Alabama, Birmingham, USA), and Dr. Sc. H. Scheffer (Department of Medical Genetics, University of Groningen, The Netherlands; current address: Department of Human Genetics, Radboud University Nijmegen Medical Center, The Netherlands) to communicate the information on the frequencies of the mutations 3272-26A࢐G and L927P in their CF population. Login to comment