ABCMdb

PMID: 19318035

Seia M, Costantino L, Paracchini V, Porcaro L, Capasso P, Coviello D, Corbetta C, Torresani E, Magazzu D, Consalvo V, Monti A, Costantini D, Colombo C
Borderline sweat test: Utility and limits of genetic analysis for the diagnosis of cystic fibrosis.
Clin Biochem. 2009 May;42(7-8):611-6. Epub 2009 Jan 24., [PubMed]

Sentences

No. Mutations Sentence Comment

57 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg74Trp ABCC7 p.Arg352Gln ABCC7 p.Arg352Gln ABCC7 p.Glu831* ABCC7 p.Glu831* ABCC7 p.Thr338Ile ABCC7 p.Ala120Thr ABCC7 p.Gln552* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Phe1052Val ABCC7 p.Arg117Cys ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Glu92Lys ABCC7 p.Arg1066His ABCC7 p.Asp614Gly ABCC7 p.Tyr1032Cys ABCC7 p.Val855Ile ABCC7 p.Val920Leu ABCC7 p.Glu1473* ABCC7 p.Thr1263Ile ABCC7 p.Gly213Glu In order to evaluate the relationship between the presence of CFTR mutation and sweat chloride concentration, we focused our attention on the 91 individuals (11.8%) in whom borderline sweat chloride values (31-59 mEq/l) were recorded (mean sweat electrolyte value was 40.0 mEq/l): 25 refused to be referred to the local Table 2 Demographic and clinical features of subjects with positive DNA analysis Patient Initials Gender Age at test years/ months Sweat chloride mEq/l Clinical indication DNA results IRT Right arm Left arm 1 CA M 49y5m 34 34 CBAVD G542X/5T-TG12 ND 2 SA M 45y2m 45 43 Pancreatitis F508del/R117H-7T ND 3 PD F 43y7m 33 38 Recurrent bronchitis F508del/5T-TG12 ND 4 CA M 36y1m 31 29 CBAVD R117H-7T/R117C-7T ND 5 SC M 36y1m 33 40 Pneumonia F508del/D1152H ND 6 MG M 25Y5m 41 45 CBAVD Q552X/D1152H NEG 7 SG M 18y5m 49 54 Pancreatitis 4016insT/dupl.prom.-3 ND 8 LS F 10y4m 41 38 Pancreatitis D1152H/L997F NEG 9 CM M 8y3m 30 31 Pneumonia F1052V/A120T NEG 10 PT M 7y3m 41 39 Positive screening F508del/Y1032C POS 11 ME F 7y1m 44 44 Positive screening 2789+5GNA/5T-TG12 POS 12 PM F 6y4m 35 36 Positive screening 2183AANG/5T-TG12 POS 13 BM F 6y3m 36 39 Positive screening F508del/5T-TG12 POS 14 CD M 5y8m 40 41 Chronic bronchitis 5T-TG12/5T-TG12 NEG 15 CG F 4y5m 33 37 Recurrent bronchitis R553X/L997F POS 16 CS F 3y8m 53 58 Family history G542X/D614G POS 17 VA M 4y2m 49 43 Pneumonia E831X/5T-TG12 ND 18 SC M 3y4m 39 39 Positive screening R352Q/G213E POS 19 CC F 2y3m 31 31 Positive screening F508del/5T-TG12 POS 20 CA F 2y5m 51 52 Recurrent bronchitis E831X/5T-TG12 ND 21 MR F 3y+7m 29 31 Family history G542X/5T-TG12 POS 22 CM F 2y3m 60 58 Pneumonia T338I/L997F POS 23 LM F 2y1m 50 52 Positive screening F508del/E1473X POS 24 CGE F 0y8m 46 47 Positive screening E92K/5T-TG13 POS 25 NF M 0y7m 32 30 Positive screening F508del/P5L POS 26 RG M 0y7m 45 40 Positive screening N1303K/P5L POS 27 PE M 47y4m 60 58 Nasal polyposis R1066H/UN ND 28 LS M 39y9m 39 38 Azoospermy N1303K/UN ND 29 TM M 38y4m 40 45 Azoospermy N1303K/UN ND 30 DF M 34y2m 52 58 Bronchiectasis 3849+10 kbCNT/UN ND 31 TV F 30y5m 35 34 Recurrent bronchitis L997F/UN ND 32 FA F 18y7m 53 49 Family history Del es.2/UN NEG 33 DG M 17y8m 43 47 Recurrent bronchitis 5T-TG12/UN NEG 34 LN F 13y7m 54 53 Nasal poliposis, malnutrition R74W-V855I/UN NEG 35 FKT M 15y4m 54 53 Chronic bronchitis R352Q/UN NEG 36 BM M 10y9m 48 51 Chronic bronchitis T1263I/UN NEG 37 SV F 11y1m 60 58 Chronic bronchitis R347H/UN NEG 38 CV F 10y10m 38 39 Recurrent bronchitis 5T-TG12/UN NEG 39 BF F 9y10m 37 38 Chronic bronchitis L997F/UN NEG 40 CA M 8y2m 33 32 Pneumonia F508del/UN NEG 41 RX F 8y7m 29 31 Chronic bronchitis V920L/UN NEG 42 MG F 4y3m 51 51 Positive screening F508del/UN POS Sweat chloride concentration and mutations/variants detected are also reported. Login to comment 59 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg74Trp ABCC7 p.Arg352Gln ABCC7 p.Arg352Gln ABCC7 p.Glu831* ABCC7 p.Glu831* ABCC7 p.Thr338Ile ABCC7 p.Ala120Thr ABCC7 p.Gln552* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Phe1052Val ABCC7 p.Arg117Cys ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Glu92Lys ABCC7 p.Arg1066His ABCC7 p.Asp614Gly ABCC7 p.Tyr1032Cys ABCC7 p.Val855Ile ABCC7 p.Val920Leu ABCC7 p.Glu1473* ABCC7 p.Thr1263Ile ABCC7 p.Gly213Glu In order to evaluate the relationship between the presence of CFTR mutation and sweat chloride concentration, we focused our attention on the 91 individuals (11.8%) in whom borderline sweat chloride values (31-59 mEq/l) were recorded (mean sweat electrolyte value was 40.0 mEq/l): 25 refused to be referred to the local Table 2 Demographic and clinical features of subjects with positive DNA analysis Patient Initials Gender Age at test years/ months Sweat chloride mEq/l Clinical indication DNA results IRT Right arm Left arm 1 CA M 49y5m 34 34 CBAVD G542X/5T-TG12 ND 2 SA M 45y2m 45 43 Pancreatitis F508del/R117H-7T ND 3 PD F 43y7m 33 38 Recurrent bronchitis F508del/5T-TG12 ND 4 CA M 36y1m 31 29 CBAVD R117H-7T/R117C-7T ND 5 SC M 36y1m 33 40 Pneumonia F508del/D1152H ND 6 MG M 25Y5m 41 45 CBAVD Q552X/D1152H NEG 7 SG M 18y5m 49 54 Pancreatitis 4016insT/dupl.prom.-3 ND 8 LS F 10y4m 41 38 Pancreatitis D1152H/L997F NEG 9 CM M 8y3m 30 31 Pneumonia F1052V/A120T NEG 10 PT M 7y3m 41 39 Positive screening F508del/Y1032C POS 11 ME F 7y1m 44 44 Positive screening 2789+5GNA/5T-TG12 POS 12 PM F 6y4m 35 36 Positive screening 2183AANG/5T-TG12 POS 13 BM F 6y3m 36 39 Positive screening F508del/5T-TG12 POS 14 CD M 5y8m 40 41 Chronic bronchitis 5T-TG12/5T-TG12 NEG 15 CG F 4y5m 33 37 Recurrent bronchitis R553X/L997F POS 16 CS F 3y8m 53 58 Family history G542X/D614G POS 17 VA M 4y2m 49 43 Pneumonia E831X/5T-TG12 ND 18 SC M 3y4m 39 39 Positive screening R352Q/G213E POS 19 CC F 2y3m 31 31 Positive screening F508del/5T-TG12 POS 20 CA F 2y5m 51 52 Recurrent bronchitis E831X/5T-TG12 ND 21 MR F 3y+7m 29 31 Family history G542X/5T-TG12 POS 22 CM F 2y3m 60 58 Pneumonia T338I/L997F POS 23 LM F 2y1m 50 52 Positive screening F508del/E1473X POS 24 CGE F 0y8m 46 47 Positive screening E92K/5T-TG13 POS 25 NF M 0y7m 32 30 Positive screening F508del/P5L POS 26 RG M 0y7m 45 40 Positive screening N1303K/P5L POS 27 PE M 47y4m 60 58 Nasal polyposis R1066H/UN ND 28 LS M 39y9m 39 38 Azoospermy N1303K/UN ND 29 TM M 38y4m 40 45 Azoospermy N1303K/UN ND 30 DF M 34y2m 52 58 Bronchiectasis 3849+10 kbCNT/UN ND 31 TV F 30y5m 35 34 Recurrent bronchitis L997F/UN ND 32 FA F 18y7m 53 49 Family history Del es.2/UN NEG 33 DG M 17y8m 43 47 Recurrent bronchitis 5T-TG12/UN NEG 34 LN F 13y7m 54 53 Nasal poliposis, malnutrition R74W-V855I/UN NEG 35 FKT M 15y4m 54 53 Chronic bronchitis R352Q/UN NEG 36 BM M 10y9m 48 51 Chronic bronchitis T1263I/UN NEG 37 SV F 11y1m 60 58 Chronic bronchitis R347H/UN NEG 38 CV F 10y10m 38 39 Recurrent bronchitis 5T-TG12/UN NEG 39 BF F 9y10m 37 38 Chronic bronchitis L997F/UN NEG 40 CA M 8y2m 33 32 Pneumonia F508del/UN NEG 41 RX F 8y7m 29 31 Chronic bronchitis V920L/UN NEG 42 MG F 4y3m 51 51 Positive screening F508del/UN POS Sweat chloride concentration and mutations/variants detected are also reported. Login to comment 90 ABCC7 p.Arg117His ABCC7 p.Asp1152His ABCC7 p.Arg117Cys It is known that some mutations as D1152H and R117H-7T/R117C-7Tare associated with negative or borderline sweat chloride value. Login to comment 92 ABCC7 p.Arg117His ABCC7 p.Asp1152His ABCC7 p.Arg117Cys ABCC7 p.Glu1473* It is known that some mutations as D1152H and R117H-7T/R117C-7Tare associated with negative or borderline sweat chloride value. Login to comment 94 ABCC7 p.Glu1473* Among the 26 subjects carrying two variants/mutations in CFTR, two (4016insT/Dup Prom-Ex3-F508del/E1473X) can be considered as CF patients according to the Consensus Statement [4] based on the presence of symptoms and two causing mutations, while for the others we can hypothesize a diagnosis of CFTR Related Disorders (CFTR-RD) [19]. Login to comment 96 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* This represents the most frequent variant in borderline subjects according to literature [4], followed by F508del (7.69%), G542X (2.31%) and N1303K (2.31%) that are the most common mutations in Caucasian population. Login to comment 97 ABCC7 p.Asp1152His ABCC7 p.Leu997Phe Moreover, we identified with a high frequency the L997F variant (3.85%) and the D1152H mutation (2.31%). Login to comment 98 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe This represents the most frequent variant in borderline subjects according to literature [4], followed by F508del (7.69%), G542X (2.31%) and N1303K (2.31%) that are the most common mutations in Caucasian population. Login to comment 99 ABCC7 p.Asp1152His ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Moreover, we identified with a high frequency the L997F variant (3.85%) and the D1152H mutation (2.31%). Login to comment 100 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe The L997F (missense substitution of leucine with phenylalanine at position 997) is a highly conserved residue in transmembrane domain. Login to comment 101 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Both heterozygosity for L997F and compound heterozygosity with other CFTR mutations have been associated with idiopathic disseminated bronchiectasis in adults, recurrent pancreatitis, and hypertrypsinemia in infants [20,21]. Login to comment 102 ABCC7 p.Asp1152His ABCC7 p.Leu997Phe Out of 5 subjects carrying the L997F variant, 4 presented pulmonary symptoms (three of them in paediatric age) and the other one pancreatitis. Login to comment 103 ABCC7 p.Leu997Phe These results suggest that paediatric patients carrying L997F, presenting with pulmonary symptoms, could become adults with disseminated bronchiectasis, if not properly followed. Login to comment 104 ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Leu997Phe The D1152H mutation is caused by a guanine to cytosine substitution at nucleic acid position 3586 of the CFTR gene, resulting in replacement of aspartic acid by histidine at amino acid 1152 of the protein. Login to comment 105 ABCC7 p.Asp1152His Out of 773 subjects who underwent sweat test, we also identified an infant carrying D1152H/F508del whose sweat value was negative. Login to comment 106 ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Leu997Phe In our borderline population, 3 subjects were compound heterozygous for D1152H with L997F, Q522X and F508del respectively. Login to comment 107 ABCC7 p.Asp1152His Out of 773 subjects who underwent sweat test, we also identified an infant carrying D1152H/F508del whose sweat value was negative. Login to comment 108 ABCC7 p.Asp1152His Based on our data, for the D1152H mutation, there appears to be an increase in sweat chloride values with age as documented for other CFTR mutations such as 3849+10 kb CNT [23]. Login to comment