ABCMdb

PMID: 23470247

Giordano S, Amato F, Elce A, Monti M, Iannone C, Pucci P, Seia M, Angioni A, Zarrilli F, Castaldo G, Tomaiuolo R
Molecular and functional analysis of the large 5' promoter region of CFTR gene revealed pathogenic mutations in CF and CFTR-related disorders.
J Mol Diagn. 2013 May;15(3):331-40. doi: 10.1016/j.jmoldx.2013.01.001. Epub 2013 Mar 5., [PubMed]

Sentences

No. Mutations Sentence Comment

41 ABCC7 p.Tyr849* of cases CF F508del/F508del Positive PI, severe L, severe P 10 CF F508del/F508del Positive PI, no L, mild P 10 CF Mutation/U Positive Variable 30 CF Mutation/mutation* Positive Severe 1 CF Mutation/TG12-T5-470V Borderline Mild 1 CF U/U Positive Variable 6 CBAVD Mutation/U Negative CBAVD alone 32 CBAVD U/U Negative CBAVD alone 6 Recurrent pancreatitis Mutation/U Negative PS, no L, no (or mild) P 11 Disseminated bronchiectasis Mutation/U Negative PS, no L, no (or mild) P 11 *The patient originally had the genotype 2789 &#fe; 5G>A/unknown; during the present study, we revealed the second mutation (ie, Y849X). Login to comment 101 ABCC7 p.Asn1303Lys The mutation was homozygous in case 1, who was also heterozygous for N1303K; however, the two other patients had the Table 4 Luciferase Expression (% Compared with the WT) of Mutated CFTR Promoter in Various Cell Types Mutation A549 PanC-1 HeLa HepG2 c.-275G>A* 106.9 (18.3) 99.5 (21.1) 106.1 (19.1) NT c.-461A>G 96.9 (11.1) 97.5 (11.1) NT 103.9 (12.1) c.-593A>G 98.6 (13.4) 82.6 (7.4) NT NT c.-674T>C* 57.1 (9.4)y 89.4 (14.1) 79.9 (24.7) 33.2 (5.7)y c.-751A>G 98.5 (7.2) 120.7 (12.7) NT 96.2 (7.1) c.-812T>G 91.4 (12.6) 83.6 (13.7) 81.6 (13.1) 145.7 (14.4)y c.-869T[8_9] 54.5 (11.6)y 53.8 (10.8)y NT 95.6 (8.9) c.-887C>T 88.5 (15.0) 112.3 (14.6) NT 97.4 (18.3) c.-1043delT 106.3 (11.6) 93.6 (11.0) 92.2 (14.1) 95.9 (14.7) c.-1308A>G 86.5 (10.6) 33.6 (11.0)y 106.2 (20.7) 95.4 (24.6) c.-1773_-1772delAT* 97.3 (9.1) 55.9 (4.5)y 135.8 (23.1) 28.9 (4.2)y c.-2200G>A* 112.8 (10.3) 105.8 (17.7) 328.0 (29.3)y 113.2 (15.5) c.-3136T>G* 97.6 (11.7) 96.3 (20.1) 116.5 (19.3) 115.0 (21.3) c.-3632G>T* 97.6 (7.4) 149.7 (10.9)y 124.0 (16.9) 64.1 (14.8)y c.-5315G>A* 102.8 (18.1) 59.7 (18.0) 100.0 (11.2) 107.1 (18.1) c.-5914A>G* 118.5 (12.2) 140.8 (15.7) 209.8 (5.7)y 100.1 (21.4) c.-5947T>G* 102.6 (12.4) 89.4 (11.1) 97.6 (18.9) 98.4 (13.6) *Novel variants. Login to comment 113 ABCC7 p.Asn1303Lys Case 6 (current age, 32 years) had the c.-1308A>G mutation and the N1303K mutation on the other allele. Login to comment 115 ABCC7 p.Gly542* Case 7 had c.-1308A>G in trans with G542X; he has PI and mild pulmonary expression. Login to comment 118 ABCC7 p.Tyr849* It was in cis with the 2789 &#fe; 5G>A mutation in case 8 (current age, 20 years), who had the 2789 &#fe; 5G>A/Y849X genotype. Login to comment 151 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Tyr849* Diagnosis Clinical expression Sweat chloride (mEq/L) CFTR genotype FEV 1% Current age (years) 1 CBAVD CBAVD alone 38 [N1303K;c.-674T>C]/c.-674T>C 90 32 2 CBAVD CBAVD alone 36 F508del/c.-674T>C 106 28 3 CBAVD CBAVD alone 36 F508del/c.-674T>C 104 30 4 CF PI, mild P, no L 70 F508del/c.-869T[8_9] 78 41 5 CF PI, mild P, nasal polyposis, chronic sinusitis, no L 76 F508del/[TG12-T5-470V; c.-1308A>G] 80 30 6 CF PI, mild P, colonization by P. aeruginosa, no L 68 N1303K/c.-1308A>G 84 32 7 CF PI, mild P, no L 71 G542X/c.-1308A>G 80 17 8 CF PI, severe P, severe L 115 [2789&#fe;5G>A;c.-1773_ -1772delAT]Y849X* 44 20 9 CF PI, mild P, no L 90 F508del/c.-1773_-1772delAT 76 28 10 CBAVD CBAVD alone 40 F508del/c.-812T>G 96 31 11 CBAVD CBAVD alone 23 F508del/c.-812T>G 102 41 12 CF PS, mild P, no L 20 F508del/[1525-1delG;TG12-T5-470V;c.-2200G>A]y 84 20 13 CF PS, mild P, no L 70 F508del/c.-3632G>T 88 26 14 CBAVD CBAVD alone 22 c.-5914A>G/U 98 *The patient originally had the genotype 2789&#fe;5G>A/unknown; during the present study, we revealed the second mutation (ie, Y849X). Login to comment 166 ABCC7 p.Tyr849* The first patient had the severe Y849X mutation23 in trans with the 2789 &#fe; 5G>A mutation. Login to comment 177 ABCC7 p.Ser549Arg On the other hand, a mutation that enhances CFTR expression and mitigates the effect of the S549R mutation has been described.26 c.-5914A>G was identified in an adult patient with a CFTR-RD with both undetected mutations who had only bronchiectasis and a borderline sweat chloride level. Login to comment