ABCMdb

PMID: 9921909

Bombieri C, Benetazzo M, Saccomani A, Belpinati F, Gile LS, Luisetti M, Pignatti PF
Complete mutational screening of the CFTR gene in 120 patients with pulmonary disease.
Hum Genet. 1998 Dec;103(6):718-22., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Glu826Lys ABCC7 p.Asp651Asn ABCC7 p.Pro1072Leu Four new mutations were identified: D651N, 2377C/T, E826K, and P1072L. Login to comment 61 ABCC7 p.Arg117His ABCC7 p.Val754Met ABCC7 p.Val754Met ABCC7 p.Asp1270Asn ABCC7 p.Asp1270Asn ABCC7 p.Ile148Thr ABCC7 p.Glu585* ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg1066Cys ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Tyr301Cys ABCC7 p.Pro111Leu ABCC7 p.Pro111Leu ABCC7 p.Met1137Val Of these 22 mutations, 14 (R75Q, P111L, R117H, I148T, Y301C, ∆F508, E585X, V754M, L997F, R1066C, M1137V, 3667ins4, D1270N, 4382delA) are listed by the Cystic Fibrosis Genetic Analysis Consortium (CFGAC) as CF mutations (CFGAC website), even if their role in CF disease remains to be proven, as is the case for R75Q, P111L, V754M, L997F, and D1270N. Login to comment 62 ABCC7 p.Arg74Trp ABCC7 p.Arg74Trp ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys ABCC7 p.Arg31Cys ABCC7 p.Ile506Val ABCC7 p.Ile506Val Five mutations (G576A, R668C, R74W, R31C, and I506V) are not thought to be the cause of CF (CFGAC website): three of them (G576A, R668C, and R74W) have been found in CBAVD patients (Anguiano et al. 1992; Chillon et al. 1995; Mercier et al. 1995; Verlingue et al. 1996), R31C was described in a DBE patient (Girodon et al. 1997), and I506V was found in the normal allele in the father of a CF child (Ghanem et al. 1994). Login to comment 63 ABCC7 p.Glu826Lys ABCC7 p.Asp651Asn ABCC7 p.Pro1072Leu Three novel mutations were first identified in this study: D651N, E826K, and P1072L. Login to comment 64 ABCC7 p.Val754Met ABCC7 p.Arg31Cys All these mutations, except V754M and R31C, affect highly conserved residues among five species investigated: human, bovine, mouse, Xenopus, and dogfish (Tucker et al. 1992). Login to comment 67 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Two compound heterozygotes were observed: G576A-R668C/L997F, and ∆F508/L997F. Login to comment 68 ABCC7 p.Leu997Phe L997F therefore is a recurrent mutation in DBE. Login to comment 69 ABCC7 p.Leu997Phe L997F was first described in a boy with borderline sweat chloride and features suggestive of cystic fibrosis (CFGAC website). Login to comment 73 ABCC7 p.Asp651Asn D651N, a G to A transition was detected at nucleotide 2083 in exon 13, which codes for the regulatory domain of CFTR. Login to comment 77 ABCC7 p.Glu826Lys E826K, a G to A substitution, was found at nucleotide 2608 in exon 13. Login to comment 80 ABCC7 p.Pro1072Leu P1072L, a C to T transition was detected at nucleotide 3347 in exon 17b, which encodes part of the second transmembrane domain. Login to comment 88 ABCC7 p.Arg117His ABCC7 p.Val754Met ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Ile148Thr ABCC7 p.Glu585* ABCC7 p.Arg75Gln ABCC7 p.Arg1066Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys ABCC7 p.Ile506Val ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Glu826Lys ABCC7 p.Tyr301Cys ABCC7 p.Pro111Leu ABCC7 p.Asp651Asn ABCC7 p.Met1137Val ABCC7 p.Pro1072Leu of cases CFTR gene PolyTb status tested mutationa DBE 23 1 G576A-R668C/L997F 7/9 1 ∆F508/L997F 9/9 1 ∆F508/- 7/9 1 R1066C/- 5/7 1 3667ins4/- 5/7 1 R75Q/- 7/7 1 M1137V/- 7/7 1 -/- 5/5 3 -/- 5/7 10 -/- 7/7 2 -/- 7/9 CB 27 1 P111L/- 7/7 1 R117H/- 7/7 1 E585X/- 7/7 1 P1072L/- 7/7 1 -/- 5/7 15 -/- 7/7 6 -/- 7/9 1 -/- 9/9 E 25 1 R668C/- 7/7 6 -/- 5/7 16 -/- 7/7 6 -/- 7/9 S 8 1 E826K/- 7/7 1 ∆F508/- 7/9 1 4382delA/- 7/7 1 L997F/- 7/9 1 V754M/- 7/9 3 -/- 7/7 LC 26 1 I148T/- 5/7 1 D1270N-R74W 5/7 1 D651N/- 7/7 1 Y301C/- 7/7 1 -/- 5/7 16 -/- 7/7 5 -/- 7/9 TB 4 1 -/- 5/7 1 -/- 7/7 2 -/- 7/9 Pneumonia 5 4 -/- 7/7 1 -/- 5/7 Pnx 2 2 -/- 7/7 Controls 68 1 L997F/- 7/9 1 R31C/- 7/7 1 I506V/- 5/7 1 -/- 5/7 1 -/- 5/9 23 -/- 7/7 4 -/- 7/9 1 -/- 9/9 2 ? Login to comment 105 ABCC7 p.Val754Met ABCC7 p.Leu997Phe ABCC7 p.Glu826Lys Two deletions (∆F508 and 4382delA, a frameshift deletion generating a stop codon 15 amino acids downstream) and three missense mutations (V754M, E826K, L997F) were detected. Login to comment 106 ABCC7 p.Val754Met All these mutations affect evolutionarily conserved residues, except V754M, which is, however, thought to be a causative mutation for CF. Login to comment 117 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp One LC patient had mutations D1270N and R74W, which have been previously described to be syntenic in a CBAVD patient (Mercier et al. 1995). Login to comment 118 ABCC7 p.Asp1270Asn D1270N is now included in the CF mutation list by the CFGAC. Login to comment 119 ABCC7 p.Arg74Trp Mutation R74W was also syntenic with the 405-46T polymorphism, as previously described (Claustres et al. 1993). Login to comment 120 ABCC7 p.Arg31Cys ABCC7 p.Ile506Val ABCC7 p.Leu997Phe Three missense mutations were detected in 33 controls: L997F, which is present in two DBE and in one sarcoidosis patients; R31C, which was first described in an apparently unaffected 6-year-old child (Ghanem et al. 1994) and next in a DBE patient (Girodon et al. 1997); I506V, which was described in a healthy parent of a CF patient who bore ∆F508 on the other chromosome (Kobayashi et al. 1990). Login to comment