ABCMdb

PMID: 22271776

Vernooij-van Langen AM, Loeber JG, Elvers B, Triepels RH, Gille JJ, Van der Ploeg CP, Reijntjens S, Dompeling E, Dankert-Roelse JE
Novel strategies in newborn screening for cystic fibrosis: a prospective controlled study.
Thorax. 2012 Apr;67(4):289-95. Epub 2012 Jan 23., [PubMed]

Sentences

No. Mutations Sentence Comment

79 ABCC7 p.Ala455Glu One infant was missed because of a low PAP concentration (0.8 mg/litre); this infant had two mutations (F508del and A455E) and a positive sweat test (chloride 65 mmol/litre). Login to comment 80 ABCC7 p.Ala455Glu One infant was missed because of a low PAP concentration (0.8 mg/litre); this infant had two mutations (F508del and A455E) and a positive sweat test (chloride 65 mmol/litre). Login to comment 104 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Ser1251Asn ABCC7 p.Leu967Ser ABCC7 p.Gln1352His Three of these infants had equivocal sweat test results (chloride 33, 34, 36 mmol/litre; all had R117H-7T as a second mutation), the other 10 had normal sweat tests (F508del/394delTT/ S1251N/R553X combined with R117H-7T n&#bc;8, F508del/L967S, F508del/Q1352H) (table 3). Login to comment 105 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Ser1251Asn ABCC7 p.Leu967Ser ABCC7 p.Gln1352His Three of these infants had equivocal sweat test results (chloride 33, 34, 36 mmol/litre; all had R117H-7T as a second mutation), the other 10 had normal sweat tests (F508del/394delTT/ S1251N/R553X combined with R117H-7T n¼8, F508del/L967S, F508del/Q1352H) (table 3). Login to comment 109 ABCC7 p.Ala455Glu ABCC7 p.Gly542* ABCC7 p.Ser1251Asn ABCC7 p.Glu730* Table 2 Immunoreactive trypsinogen and pancreatitis-associated protein concentrations, CFTR gene mutation analysis and sweat tests in infants with cystic fibrosis detected by newborn screening IRT (mg/litre) PAP (mg/litre) Mutation 1 Mutation 2 Sweat test chloride (mmol/litre) 1 438 5.3 F508del F508del 74 2 284 1.8 F508del F508del 88 3 266 9.8 F508del F508del 97 4 237 1.8 F508del F508del 11 and 74 5 197 4.3 F508del F508del 69 6* 191 12.6 F508del C.3889dupT 94 7 164 14.4 F508del G542X 102 8 129 4.3 F508del F508del Failed 9 110 2.2 F508del F508del 94 10 109 2.0 F508del F508del 51 11 105 4.4 F508del F508del 149 12 155 2.6 F508del F508del 111 13 191 12.6 F508del F508del 4 14 116 15.8 F508del F508del Failed 3 times 15 293 5.7 F508del 2184A 120 16* 228 15.8 F508del 1294_1300del 99 17 218 4.5 F508del G85E 99 18 153 4.0 F508del S1251N 77 19* 141 15.8 F508del E730X 82 20z 78 0.8 F508del A455E 65 21y 114 11.2 F508del F508del Failed 22y 109 0.8 F508del F508del 78 23y 93 1.3 F508del F508del e 24y 75 6.7 F508del F508del 78 *Second mutation detected by sequencing. Login to comment 110 ABCC7 p.Ala455Glu ABCC7 p.Gly542* ABCC7 p.Ser1251Asn ABCC7 p.Glu730* Table 2 Immunoreactive trypsinogen and pancreatitis-associated protein concentrations, CFTR gene mutation analysis and sweat tests in infants with cystic fibrosis detected by newborn screening IRT (mg/litre) PAP (mg/litre) Mutation 1 Mutation 2 Sweat test chloride (mmol/litre) 1 438 5.3 F508del F508del 74 2 284 1.8 F508del F508del 88 3 266 9.8 F508del F508del 97 4 237 1.8 F508del F508del 11 and 74 5 197 4.3 F508del F508del 69 6* 191 12.6 F508del C.3889dupT 94 7 164 14.4 F508del G542X 102 8 129 4.3 F508del F508del Failed 9 110 2.2 F508del F508del 94 10 109 2.0 F508del F508del 51 11 105 4.4 F508del F508del 149 12 155 2.6 F508del F508del 111 13 191 12.6 F508del F508del 4 14 116 15.8 F508del F508del Failed 3 times 15 293 5.7 F508del 2184A 120 16* 228 15.8 F508del 1294_1300del 99 17 218 4.5 F508del G85E 99 18 153 4.0 F508del S1251N 77 19* 141 15.8 F508del E730X 82 20z 78 0.8 F508del A455E 65 21y 114 11.2 F508del F508del Failed 22y 109 0.8 F508del F508del 78 23y 93 1.3 F508del F508del e 24y 75 6.7 F508del F508del 78 *Second mutation detected by sequencing. Login to comment 135 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Ser1251Asn ABCC7 p.Glu60* ABCC7 p.Leu967Ser ABCC7 p.Gln1352His CF, cystic fibrosis; IRT, immunoreactive trypsinogen; PAP, pancreatitis-associated protein. Table 3 Immunoreactive trypsinogen and pancreatitis-associated protein concentrations, CFTR gene mutation analysis and sweat tests for all infants with an equivocal diagnosis IRT (mg/litre) PAP (mg/litre) Mutation 1 Mutation 2 Sweat test chloride (mmol/litre) 1 199 1.4 E60X R117H-7T 36 2 139 0.8 394delTT R117H-7T/9T 21 3 123 0.6 F508del R117H-7T 22 4 89 1.4 S1251N R117H-7T 29 5 79 1.6 F508del R117H-7T 26 6 77 2.4 R553X R117H-7T 22 7 76 0.8 F508del R117H-7T 34 8 73 0.5 F508del R117H-7T 25 9 70 1.0 F508del R117H-7T 22 10 69 1.1 F508del R117H-7T 33 11 67 2.7 F508del R117H-7T 17 12* 174 3.8 F508del L967S 19 13* 84 3.2 F508del Q1352H 17 Equivocal diagnosis&#bc;two CFTR gene mutations of which one has unclear clinical significance, and a normal or equivocal sweat test result. Login to comment 136 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Ser1251Asn ABCC7 p.Glu60* ABCC7 p.Leu967Ser ABCC7 p.Gln1352His CF, cystic fibrosis; IRT, immunoreactive trypsinogen; PAP, pancreatitis-associated protein. Table 3 Immunoreactive trypsinogen and pancreatitis-associated protein concentrations, CFTR gene mutation analysis and sweat tests for all infants with an equivocal diagnosis IRT (mg/litre) PAP (mg/litre) Mutation 1 Mutation 2 Sweat test chloride (mmol/litre) 1 199 1.4 E60X R117H-7T 36 2 139 0.8 394delTT R117H-7T/9T 21 3 123 0.6 F508del R117H-7T 22 4 89 1.4 S1251N R117H-7T 29 5 79 1.6 F508del R117H-7T 26 6 77 2.4 R553X R117H-7T 22 7 76 0.8 F508del R117H-7T 34 8 73 0.5 F508del R117H-7T 25 9 70 1.0 F508del R117H-7T 22 10 69 1.1 F508del R117H-7T 33 11 67 2.7 F508del R117H-7T 17 12* 174 3.8 F508del L967S 19 13* 84 3.2 F508del Q1352H 17 Equivocal diagnosis¼two CFTR gene mutations of which one has unclear clinical significance, and a normal or equivocal sweat test result. Login to comment 163 ABCC7 p.Arg117His Eleven of the 13 infants with an equivocal diagnosis in the IRT/DNA/sequencing strategy had R117H-7T as a second mutation. Login to comment 164 ABCC7 p.Arg117His Eleven of the 13 infants with an equivocal diagnosis in the IRT/DNA/sequencing strategy had R117H-7T as a second mutation. Login to comment 165 ABCC7 p.Arg117His The Dutch CF Registry showed only 10 patients (1196 registered patients in 2008) with a R117H-7T mutation, and only four of them were diagnosed under the age of 18 years. Login to comment 166 ABCC7 p.Arg117His The Dutch CF Registry showed only 10 patients (1196 registered patients in 2008) with a R117H-7T mutation, and only four of them were diagnosed under the age of 18 years. Login to comment 167 ABCC7 p.Arg117His This indicates that this mutation mostly acts as a non-disease-causing variant.30 31 Many experts on NBS for CF therefore advise exclusion of this mutation.31 If R117H-7Twere to be excluded from the panel, only two infants with an equivocal diagnosis would have been identified with this strategy. Login to comment 168 ABCC7 p.Arg117His This indicates that this mutation mostly acts as a non-disease-causing variant.30 31 Many experts on NBS for CF therefore advise exclusion of this mutation.31 If R117H-7Twere to be excluded from the panel, only two infants with an equivocal diagnosis would have been identified with this strategy. Login to comment