ABCMdb

PMID: 12955726

Feldmann D, Couderc R, Audrezet MP, Ferec C, Bienvenu T, Desgeorges M, Claustres M, Mittre H, Blayau M, Bozon D, Malinge MC, Monnier N, Bonnefont JP, Iron A, Bieth E, Dumur V, Clavel C, Cazeneuve C, Girodon E
CFTR genotypes in patients with normal or borderline sweat chloride levels.
Hum Mutat. 2003 Oct;22(4):340., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC7 p.Arg117His ABCC7 p.Gly149Arg ABCC7 p.Leu206Trp ABCC7 p.Ser1235Arg ABCC7 p.Ser945Leu ABCC7 p.Asp1152His ABCC7 p.Arg1070Trp R117H, D1152H, L206W, 3272-26A>G, S1235R, G149R, R1070W, S945L, and the poly-T tract variation commonly called IVS8-5T were also observed. Login to comment 18 ABCC7 p.Arg117His ABCC7 p.Gly551Ser ABCC7 p.Leu206Trp ABCC7 p.Asp1152His Other mutations that might be associated with intermediate (40-60 mmol/L) or normal sweat chloride values have been reported: R117H [Kerem et al., 1997; Massie et al., 2000], G551S [Strong et al., 1991], A455E [Gan et al., 1995], L206W [Desgeoges et al., 1995], D1152H [Feldmann et al., 1995; Lebecque et al., 2001]. Login to comment 44 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg347Pro ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly149Arg ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Arg1070Gln ABCC7 p.Ser1235Arg ABCC7 p.Ser945Leu ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Gly91Arg ABCC7 p.Arg1070Trp Table 1 : Genotypes and Phenotypes of Patients with Normal or BordIerline Sweat Tests Patient Age at diagnosis (years) CFTR GENOTYPE* Allele 1 Allele 2 SWEAT CL- MEAN (MMOL/L) PHENOTYPE 1 0.2 F508del G149R 38 P+PI, neonatal hypertrypsinemia, 2 0.3 G551D R117H-7T 31 neonatal hypertrypsinemia 3 0.4 F508del R1070W 30.5 neonatal hypertrypsinemia 4 0.4 F508del R117H-7T 52 P 5 0.6 F508del 3849+10kbC>T 48 P 6 0.11 F508del S945L 58 P+PI 7 1 F508del 5T 40 P+CBAVD 8 2 F508del L206W 53 P 9 2 W1282X 5T 42.5 P 10 5 F508del 3849+10kbC>T 55.5 P 11 5 F508del L206W 55 P 12 5 G91R 5T 47.5 P 13 6 G551D S1235R+5T 49.5 P, neonatal hypertrypsinemia 14 7 F508del 3849+10kb 50 P, nasal popyposis 15 13 F508del R117H-7T 58 P, nasal polyposis 16 18 F508del 5T 60.5 P 17 20 G542X 3849+10kbC>T 52 P+PI 18 21 I507del 3849+10kbC>T 54 P, bronchiectasis 19 30 R347P 3849+10kbC>T 43 P, Pseudomonas colonisation 20 30 I507del L206W 57.5 CBAVD, chronic cough 21 31 F508del R117H-7T 60 CBAVD 22 32 G542X 3849+10kbC>T 30 P, Pseudomonas colonisation 23 34 F508del 3272-26A>G 64 P, CBAVD 24 37 R1070Q D1152H 56 CBAVD, bronchectasis 25 46 F508del D1152H 43 P 26 55 F508del D1152H 48 P, Pseudomonas colonisation 27 56 I507del S1235R 53 P 28 >18 F508del D1152H 60 P+PI 29 >20 F508del 3849+10kbC>T 18 P, bronchiectasis 30 >20 F508del 3272-26A>G 61 P *All mutations are named in accordance with the numbering used in the CFTR Mutation Database: http://www.genet.sickkids.on.ca/cftr/. Login to comment 52 ABCC7 p.Arg117His ABCC7 p.Leu206Trp ABCC7 p.Asp1152His Other common mutations observed in our study such as 3849+10kbC>T, R117H, D1152H, L206W were found at a low prevalence in typical CF patients (0.4 % to 0.2 %). Login to comment 56 ABCC7 p.Ser1235Arg One patient had a complex allele with S1235R and IVS8(5T). Login to comment 76 ABCC7 p.Arg347Pro In this study, 3849+10kbC>T was observed in four adults and three children with a severe allele in trans and in one adult with R347P/3849+10kbC>T. Login to comment 82 ABCC7 p.Arg117His ABCC7 p.Leu206Trp ABCC7 p.Asp1152His Other common mutations observed in our study were R117H, IVS8(5T), D1152H, and L206W. Login to comment 83 ABCC7 p.Arg117His Usually, in patients with typical CF, R117H alleles also bear the 5T-splice variant [Kiesewetter et al., 1993; Friedman et al., 1997]. Login to comment 84 ABCC7 p.Arg117His In our study, none of the patients carried the R117H-5T allele. Login to comment 85 ABCC7 p.Arg117His Massie et al. [2000] and Padoan et al. [2002] have reported patients with R117H and an elevated IRT with a normal sweat test. Login to comment 88 ABCC7 p.Arg117His Recently, Lebecque et al. [2002] reported on two patients with sinopulmonary disease and R117H-7T in trans of a severe mutation. Login to comment 89 ABCC7 p.Arg117His It is possible that not only the 5T-splice variant, but also other genetic variations may modulate the phenotype of the R117H mutant. Login to comment 92 ABCC7 p.Ser1235Arg We have observed four patients with the IVS8(5T) variant and a severe mutation in trans and one patient with the complex allele S1235R-5T. Login to comment 97 ABCC7 p.Asp1152His The D1152H mutation has been observed in men with CBAVD [Claustres et al., 2000] but also in adults with mild pulmonary disease [Feldmann et al., 1995]. Login to comment 98 ABCC7 p.Asp1152His This mutation, combined with a second CFTR mutation, has also been observed by Lebecque et al. [2002] and Groman et al. [2002] associated with intermediate sweat tests and documented pulmonary symptoms in respectively two patients. We observed four adults with D1152H, the age of two of the patients (55 and 46 years) suggests an unusual course of the disease. Login to comment 99 ABCC7 p.Leu206Trp Previous reports on L206W suggested that this mutation caused CBAVD or mild pulmonary disease [Rozen, 1995; Desgeorges, 1995]. Login to comment 100 ABCC7 p.Leu206Trp In our study, L206W with F508del in trans was observed in a patient with CBAVD, but also in one patient with pancreatic insufficiency. Login to comment 101 ABCC7 p.Gly149Arg ABCC7 p.Ser1235Arg ABCC7 p.Ser945Leu ABCC7 p.Arg1070Trp The other mutations observed in trans of severe mutations were G149R, R1070W, S945L and S1235R. Login to comment 102 ABCC7 p.Gly149Arg ABCC7 p.Ser1235Arg ABCC7 p.Arg1070Trp G149R and R1070W mutations have been previously described in CBAVD patients [Mercier et al., 1995; Jezequel et al., 2000] and S1235R have been described associated with variable pulmonary symptoms and occasionally borderline sweat tests [Monagham et al., 2000]. Login to comment 103 ABCC7 p.Ser945Leu But, S945L previously reported in CF patient, was observed in this study in one patient with borderline sweat test. Login to comment 104 ABCC7 p.Ser945Leu The large cohort of patients studied in this work can help the screening of CFTR mutations in patients with the selected phenotype and of all the mutations described in this work, at least two mutations, 3272-26A/G and S945L, were observed for the first time in patients with borderline sweat chloride values. Login to comment