ABCMdb

PMID: 15173476

Comeau AM, Parad RB, Dorkin HL, Dovey M, Gerstle R, Haver K, Lapey A, O'Sullivan BP, Waltz DA, Zwerdling RG, Eaton RB
Population-based newborn screening for genetic disorders when multiple mutation DNA testing is incorporated: a cystic fibrosis newborn screening model demonstrating increased sensitivity but more carrier detections.
Pediatrics. 2004 Jun;113(6):1573-81., [PubMed]

Sentences

No. Mutations Sentence Comment

78 ABCC7 p.Arg117His ABCC7 p.Phe508Cys ABCC7 p.Ile506Val ABCC7 p.Ile507Val DNA Amplification and colorimetric detection on linear array strips with Analyte Specific Reagents for a 16-mutation assay (gift from Roche Molecular Systems, Alameda, CA) and a 27-mutation assay (Linear Array CF-31; Roche Molecular Biochemicals, Indianapolis, IN) were used.20 For both panels, the DNA assay assessed only CFTR mutations; detection of polymorphisms was incorporated as a reflex test for confirmation of putative ⌬F508 homozygotes (assay for F508C, I506V, and I507V) or for genotype elucidation on detection of 2 mutations including R117H (assay for IVS8polyT 5/7/9T). Login to comment 79 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr The 16-mutation panel included ⌬F508, R117H, G551D, G542X, W1282X, N1303K, R334W, 621 ϩ 1GϾT, R553X, ⌬I507, 1717-1GϾA, R347P, R560T, 3849 ϩ 10kbCϾT, A455E, and S549N. Login to comment 80 ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Ser1255* ABCC7 p.Gly480Cys ABCC7 p.Ala559Thr The 27-mutation panel included all of the 16 except S549N and the following additional mutations: 3120 ϩ 1GϾA, 3659delC, A559T, R1162X, S1255X, 405 ϩ 3AϾC, 711 ϩ 1GϾT, 2789 ϩ 5GϾA, G480C, 2307insA, G85E, and 1078delT. Login to comment 122 ABCC7 p.Arg117His ABCC7 p.Gly542* False-Negative Results One of the 2 infants who were not detected by the Ͼ95th daily percentile screen had an IRT value at the 93.9th percentile and meconium ileus (positive sweat test; G542X/unknown); the other infant missed by the screen had an IRT value at the 84th percentile and presented at 2 months with failure to thrive and upper respiratory tract infection (positive sweat test; ⌬F508/R117H). Login to comment 126 ABCC7 p.Gly542* The 15th infant`s IRT did not prompt a DNA assay; subsequent diagnostic testing revealed no ⌬F508 mutation but detected another (G542X) that is included in our multiple-CFTR-mutation testing panel. Login to comment 133 ABCC7 p.Arg117His ABCC7 p.Ser1235Arg † An additional 2 infants have been shown to have 2 CFTR DNA variants when mother`s prenatal DNA testing on a subsequent pregnancy prompted infant genotyping; neither infant meets CFF criteria for diagnosis (one is ⌬F508/S1235R, has sweat-test-negative results, and is well; the other is ⌬F508/R117H 7T/7T, has sweat-test-borderline results, and is well). Login to comment 141 ABCC7 p.Gly85Glu One of these carries a mutation (G85E) that was not included on the 16-mutation panel (used at the time of testing) but is on the 27-mutation panel. Login to comment 142 ABCC7 p.Arg117Cys This infant also carries a mutation (R117C) that is not present on either panel or on the population-screening panel recommended by the American College of Medical Genetics.26 The other 2 CF-affected infants presumably have CFTR mutations not yet identified. Login to comment 150 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Leu206Trp ABCC7 p.Gly85Glu ABCC7 p.Arg117Cys ABCC7 p.Arg117Cys 112 CF-Affected MA Infants Who Were Screened: Details of CF Newborn Screening Results and Diagnostic Follow-up Sweat Test Result (mEq Cl-/L) CF-Screen Positive CF-Screen Negative Total 2 Mutations 1 Mutation 0 Mutations Positive (Ն60) 62 19 3 2 86 Borderline (Ն30 and Ͻ60) Within expectations for specific CF genotype* 5 3 8¶ Monozygotic twin sweat test positive† 1 1 Negative (Ͻ30) Within expectations for specific CF genotype‡ 4 1 5 Incomplete (not done or QNS) 2 CFTR mutations identified and clinical symptoms§ 6 1 7 2 CFTR mutations identified without clinical symptoms࿣ 5 5 Total 82 25 3 2 112 * ⌬F508/R117H;7T (3), ⌬F508/3849 ϩ 10kb (2), ⌬F508/L206W (1), G551D/R117C (1), and G85E/R117C (1). Login to comment 154 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Gly85Glu ABCC7 p.Asp1152His ‡ ⌬F508/D1152H, ⌬F508/R117H (2), G85E/R117H, and G551D/R117H. Login to comment 155 ABCC7 p.Arg1066Cys § Three infants died with CF diagnosis before sweat testing (including 1 infant with only 1 mutation detected by the screen and R1066C detected by additional analysis); 5 other infants had 2 CFTR mutations detected by the screen and clinical symptoms. Login to comment 159 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Leu206Trp ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Arg1066Cys ABCC7 p.Tyr1092* ABCC7 p.Arg117Cys ABCC7 p.Arg117Cys Genotypes and Frequencies Observed in 112 CF-Affected Infants First Mutation Second Mutation N ⌬F508 ⌬F508 55 ⌬F508 R117H 7* ⌬F508 G551D 4 ⌬F508 N1303K 3 ⌬F508 W1282X 3 ⌬F508 G542X 2 ⌬F508 1898 ϩ 1 G Ͼ A 2 G85E R117C 2 ⌬F508 1717-GϾA 1 ⌬F508 3849 ϩ 10kbC Ͼ T 1 ⌬F508 R1066C 1 ⌬F508 Y1092X 1 ⌬F508 L206W 1 ⌬F508 R560T 1 ⌬F508 1152H 1 ⌬F508 621 ϩ 1G Ͼ T 1 R117H G551D 1 R117H G85E 1 G551D 2789 ϩ 5GϾA 1 G551D R117C 1 G85E 711 ϩ 1GϾT 1 W1282X 3849 ϩ 10kbCϾT 1 R553X 2183AAϾG 1 A455E S549R 1 ⌬F508 Unknown† 13 N1303K Unknown 2 G542X Unknown 1 Unknown Unknown 2 * Includes 1 of the false-negative screens. Login to comment 170 ABCC7 p.Leu206Trp ABCC7 p.Arg1066Cys ABCC7 p.Tyr1092* ABCC7 p.Asp1152His § Presumed second CFTR mutation: R1066C, 1898GϾA (2), D1152H, L206W, Y1092X, and "not present in additional mutation analysis and yet to be identified" (13). Login to comment 171 ABCC7 p.Ser549Arg ABCC7 p.Arg117Cys ࿣ Presumed second CFTR mutation: 2183AAϾG, R117C (2), S549R, and "not present in additional mutation analysis and yet to be identified" (2). Login to comment 173 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Arg117Cys # One infant`s genotype: G85E/R117C screening done with 16-mutation panel before inclusion of G85E in the 27-mutation panel; other 2 infant`s genotypes: "not present in additional mutation analysis and yet to be identified" for the 2 alleles. Login to comment