ABCMdb

PMID: 15463882

Hubert D, Fajac I, Bienvenu T, Desmazes-Dufeu N, Ellaffi M, Dall'ava-Santucci J, Dusser D
Diagnosis of cystic fibrosis in adults with diffuse bronchiectasis.
J Cyst Fibros. 2004 Mar;3(1):15-22., [PubMed]

Sentences

No. Mutations Sentence Comment

47 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Val520Phe ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Tyr122* ABCC7 p.Arg560Thr We used an oligonucleotide ligation assay using a commercially available kit (Cystic Fibrosis Assay, Applied Biosystems, Foster City, CA, USA) to seek 31 mutations in the CFTR gene (F508del, I507del, Q943X, V520F, 1717y1GࡊA, G542X, G551D, R553X, R560T, S549R, S549 N, 3849q10kbCࡊT, 3849q4AࡊG, R1162X, 3659delC, W1282X, 3905insT, 621q1GࡊT, R117H, Y122X, 711q1GࡊT, 1078delT, R347P, R347H, R334 W, A455E, N1303K, G85E, 1898q1GࡊA, 2183AAࡊG, 2789q5GࡊA) which allowed to detect 82% of the CF alleles in France. Login to comment 128 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly85Glu The consensus opinion is Table 3 Sensitivity of the sweat test and genotyping for the diagnosis of cystic fibrosis Positive diagnosis of CF Number of patients (percentage) Sweat test (sweat chloride)60 mmol l ) y1 37 (80%) Molecular analysis: -screening for 31 mutations 18 (39%) -complete screening 36 (78%) Combination of sweat test and molecular analysis: -sweat testqscreening for 31 mutations 42 (91%) -sweat testqcomplete screening 45 (98%) Table 4 Efficacy of the CFTR genetic analysis according to the screening method used Identified mutations Two mutations At least one mutation No mutations Screening for F508del Number of patients (%) 3 (7%) 31 (67%) 15 (33%) Screening for nine mutations* Number of patients (%) 6 (13%) 36 (78%) 10 (22%) Screening for 31 mutations** Number of patients (%) 18 (39%) 43 (93%) 3 (7%) Complete screening Number of patients (%) 36 (78%) 46 (100%) 0 Nine mutations: F508del, I507del, G542X, G551D, R553X, 621q1GࡊT, G85E, R117H, N1303K. Login to comment 129 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln493* ABCC7 p.Val520Phe ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Tyr122* ABCC7 p.Arg560Thr * 31 mutations: F508del, I507del, Q493X, V520F, 1717y1GࡊA, G542X, G551D, R553X, R560T, S549R, S549 N, 3849q10kbCࡊT, 3849q ** 4AࡊG, R1162X, 3659delC, W1282X, 3905insT, 621q1GࡊT, R117H, Y122X, 711q1GࡊT, 1078delT, R347P, R347H, R334 W, A455E, N1303K, G85E, 1898q1GࡊA, 2183AAࡊG, 2789q5GࡊA. that the laboratory criteria for the diagnosis of CF should be expanded to include identification of CFTR mutations and abnormal bioelectrical properties of the nasal epithelium, in addition to the sweat test w7x. Login to comment 135 ABCC7 p.Gly551Ser However, it is now clear that some CF mutations are associated with normal sweat chloride values, as described for the 3849q10kbCࡊT w22x and G551S mutations w23x. Login to comment 141 ABCC7 p.Ser1235Arg The S1235R mutation was also found in one of our patients who had a negative sweat test, but chronic bronchial colonization with P. aeruginosa and obstructive azoospermia. Login to comment 142 ABCC7 p.Ser1235Arg Monaghan et al. w26x suggested that S1235R is pathogenic when combined with a second CF mutation, although phenotypic manifestations appear to be variable. Login to comment 148 ABCC7 p.Gly542* The F508del mutation was found in 31 patients and the G542X mutation was found in five patients. Login to comment 149 ABCC7 p.Ala455Glu The next most frequent mutations were the 2183AAࡊG, 3849q10kbCࡊT, 3272y26AࡊG, A455E and 2789q5GࡊA mutations, which were all found in at least three patients. Login to comment 150 ABCC7 p.Ala455Glu The 3849q10kbCࡊT, 3272y26A)G, A455E and 2789q 5GࡊA mutations belong to the class V of CFTR mutations, which result in residual levels of CFTR transcripts and protein w17,24x. Login to comment 151 ABCC7 p.Ala455Glu The A455E missense mutation is associated with mild lung disease w27x, whereas the 3272y26AࡊG w28x, 2789q5GࡊA w29x and 3849q10kbCࡊT w22x mutations are associated with a milder CF phenotype. Login to comment