PMID: 15371908

Buyse IM, McCarthy SE, Lurix P, Pace RP, Vo D, Bartlett GA, Schmitt ES, Ward PA, Oermann C, Eng CM, Roa BB
Use of MALDI-TOF mass spectrometry in a 51-mutation test for cystic fibrosis: evidence that 3199del6 is a disease-causing mutation.
Genet Med. 2004 Sep-Oct;6(5):426-30., [PubMed]
Sentences
No. Mutations Sentence Comment
0 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:0:589
status: NEW
view ABCC7 p.Ile148Thr details
Use of MALDI-TOF mass spectrometry in a 51-mutation test for cystic fibrosis: Evidence that 3199del6 is a disease-causing mutation Inge M. Buyse, PhD1 , Sarah E. McCarthy1 , Paul Lurix, PhD1 , Robert P. Pace, MS1 , David Vo1 , George A. Bartlett1 , Eric S. Schmitt, PhD, MS1 , Patricia A. Ward, MS1 , Christopher Oermann, MD2 , Christine M. Eng, MD1 , and Benjamin B. Roa, PhD1 Purpose: We developed a 51-mutation extended cystic fibrosis (CF) panel that incorporates the 25 previously recommended CFTR mutations, plus 26 additional mutations including 3199del6, which was associated with I148T. Login to comment
2 ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:2:139
status: NEW
view ABCC7 p.Gly542* details
Results: CF testing was performed on over 5,000 individuals, including a 3-year-old Hispanic-American patient with a compound heterozygous G542X/3199del6 genotype. Login to comment
3 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:3:19
status: NEW
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He is negative for I148T, or other mutations assessed by CFTR gene sequencing. Login to comment
7 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:7:876
status: NEW
view ABCC7 p.Ile148Thr details
The disease-causing CFTR gene lies on chromosome 7q31.2 and was cloned in 1989.1-3 The clinical spectrum ranges from a severe CF phenotype characterized by progressive lung disease, pancreatic insufficiency, male infertility, and elevated sweat chloride, to a milder presentation that includes congenital bilateral absence of the vas deferens (CBAVD) in males.4 Over 1300 CFTR mutations have been identified to date, wherein certain mutations are correlated with a mild or severe clinical phenotype.5 CF carrier screening for couples of reproductive age is recommended in the U.S. using a core panel of 25 common CF mutations.6 Although laboratories vary in the number of mutations and methodologies used for CF testing, many labs offer a CF testing panel that is applied to both carrier screening and diagnostic cases. One controversial component of the recommended panel is I148T, which was initially classified as a severe CF mutation. Login to comment
8 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:8:86
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:8:162
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:8:420
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:8:437
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:8:541
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:8:843
status: NEW
view ABCC7 p.Ile148Thr details
However, in vitro studies indicated that the major CFTR functions are retained by the I148T protein.7 Population screening studies revealed that the frequency of I148T is approximately 100-fold greater in asymptomatic carriers versus CF patients, which is more consistent with a benign variant than a disease-causing mutation.8,9 An in-frame deletion in exon 17a, 3199del6, was previously identified in association with I148T; moreover, I148T was found to be associated with a severe CF phenotype only when present in a complex haplotype of I148T/3199del6/9T, paired with a severe CF mutation on the opposite chromosome.4,8 The clinical significance of the 3199del6/I148 haplotype is unclear from the limited data available, because the few laboratories that test for 3199del6 mostly do reflex testing limited to patients who are positive for I148T. Login to comment
12 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:12:89
status: NEW
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Moreover, our testing strategy evaluates each patient`s 3199del6 status independently of I148T, which is useful for refining genotype-phenotype correlations. Login to comment
18 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:18:60
status: NEW
view ABCC7 p.Ile148Thr details
An additional 11 patients who were previously identified as I148T carriers by allele-specific oligonucleotide (ASO) anal- From the 1 Medical Genetics Laboratories, Department of Molecular and Human Genetics, and the 2 Department of Pediatrics, Baylor College of Medicine, Houston, Texas. Login to comment
28 ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15371908:28:79
status: NEW
view ABCC7 p.Arg117His details
In compliance with ACMG recommendations, this assay provides reflex testing on R117H positive samples for the 5T, 7T, and 9T polymorphic alleles at the intron 8 polythymidine tract.6 Robotic automation was applied at the pre-PCR (Multiprobe II HT, Perkin Elmer and Biomek FX, Beckman) and post-PCR processes (Multimek, Beckman). Login to comment
39 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:39:105
status: NEW
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ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:39:184
status: NEW
view ABCC7 p.Ile148Thr details
Statistical analysis The observed CF carrier frequency in our screening population, and the frequency of I148T in particular, were statistically compared to previously reported CF and I148T carrier frequencies8 using the Fisher exact test, with a two-sided P-value reported. Login to comment
40 ABCC7 p.Glu60*
X
ABCC7 p.Glu60* 15371908:40:459
status: NEW
view ABCC7 p.Glu60* details
RESULTS CFTR mutation panel analysis Our expanded CF assay using a MALDI-TOF mass spectrometry system (Sequenom) was initially validated against the ASO hybridization assay that was previously implemented in our laboratory.11 A total of 1080 patient samples that were analyzed by ASO were tested in parallel by MALDI-TOF mass spectrometry, and concordant results were obtained with the exception of two cases. One sample was heterozygous for a rare mutation, E60X, which was not included in the smaller (37 mutation) ASO panel. Login to comment
41 ABCC7 p.Gly314Glu
X
ABCC7 p.Gly314Glu 15371908:41:52
status: NEW
view ABCC7 p.Gly314Glu details
ABCC7 p.Gly314Ala
X
ABCC7 p.Gly314Ala 15371908:41:156
status: NEW
view ABCC7 p.Gly314Ala details
In the second case, an ASO result of a heterozygous G314E mutation was further characterized by MALDI-TOF mass spectrometry as a different allelic variant, G314A (data not shown). Login to comment
42 ABCC7 p.Gly314Ala
X
ABCC7 p.Gly314Ala 15371908:42:36
status: NEW
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DNA sequence analysis confirmed the G314A allele, which is a novel missense variant of inconclusive clinical significance. Login to comment
45 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:45:17
status: NEW
view ABCC7 p.Ile148Thr details
positives (Freq) I148T 3199del6 4839 Carrier screening 173 (3.5% Ϸ1/28) 16 1 155 Diagnostic 30 (19.4% Ϸ1/5) 0 1 34 Parental/FEBa 3 (8.8%) 1 0 10 Prenatal study 5 (50%)b 0 0 53 Family history 20 (37.7%) 0 0 277 Not specified 10 (3.6%) 0 0 a Fetal echogenic bowel b Either heterozygous or homozygous positive for parental mutations. Login to comment
46 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:46:37
status: NEW
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Table 2 Description of 28 identified I148T heterozygous individualsa No. Login to comment
47 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:47:365
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:47:479
status: NEW
view ABCC7 p.Ile148Thr details
Genotype Indication EthnicityI148T 3199del6 Others 1 ϩ - - Diagnostic Not specified 1 ϩ - ⌬F508 Parental FEBb Caucasian 18 ϩ - - Carrier screen Caucasian 1 ϩ - - Carrier screen Asian Indian 4 ϩ - - Carrier screen Not specified 2 ϩ - - Not specified Not specified 1 ϩ ϩ - Carrier screen Caucasian a Includes 17 I148T carriers found in a consecutive dataset by MALDI-TOF Mass Spectrometry (also contributed to ref 14), and 11 I148T carriers previously identified by ASO analysis. Login to comment
55 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:55:55
status: NEW
view ABCC7 p.Ile148Thr details
We observed a disproportionately high frequency of the I148T allele among heterozygous carriers with no family history (16/173 CF carriers), compared to patients referred with a definite or possible diagnosis of CF (0/155 CF patients). Login to comment
56 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:56:56
status: NEW
view ABCC7 p.Ile148Thr details
Our findings are consistent with significantly elevated I148T allele frequencies in asymptomatic carriers versus CF patients by previous reports.8,9 In addition, two patients out of 5368 consecutive cases were found to be positive for 3199del6 (Table 1), and details on these two cases are provided in the following sections. Login to comment
57 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:57:15
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:57:106
status: NEW
view ABCC7 p.Ile148Thr details
Description of I148T-positive individuals A composite group of 28 individuals who tested positive for the I148T allele is listed in Table 2. Login to comment
58 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:58:97
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:58:136
status: NEW
view ABCC7 p.Ile148Thr details
This group included 17 individuals in our consecutive dataset who were simultaneously tested for I148T and 3199del6, plus 11 additional I148T carriers who were previously identified by ASO and subsequently tested by MALDI-TOF. Login to comment
59 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:59:78
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:59:125
status: NEW
view ABCC7 p.Ile148Thr details
Population screening was the indication for testing among the majority of the I148T carriers (24 out of 28); among these, 23 I148T carriers tested negative for 3199del6. Login to comment
60 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:60:119
status: NEW
view ABCC7 p.Ile148Thr details
One individual of European Caucasian descent referred to our lab for carrier screening was genotyped positive for both I148T and 3199del6. Login to comment
61 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:61:34
status: NEW
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However, the configuration of the I148T and 3199del6 alleles could not be determined on this asymptomatic individual because parental samples were not submitted for analysis. Login to comment
62 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:62:22
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:62:183
status: NEW
view ABCC7 p.Ile148Thr details
Of the four remaining I148T carriers who were referred for reasons other than carrier screening, one was a male patient with obstructive azoospermia who was heterozygous positive for I148T and negative for the 3199del6 and 5T alleles. Login to comment
64 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:64:41
status: NEW
view ABCC7 p.Ile148Thr details
She tested heterozygous positive for the I148T and ⌬F508 mutations, and negative for the 3199del6 and the 5T alleles (9T/9T). Login to comment
66 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:66:107
status: NEW
view ABCC7 p.Ile148Thr details
These findings are consistent with reports of apparently healthy individuals with a ⌬F508-positive, I148T-positive, and 3199del6-negative genotype.8,9 This individual`s spouse was also referred for testing and found to be negative for 51 CF mutations and the 5T allele (7T/7T). Login to comment
67 ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:67:38
status: NEW
view ABCC7 p.Gly542* details
Identification of a CF patient with a G542X/3199del6 genotype In the course of clinical testing with the extended CF panel, we studied a 3-year old Hispanic-American male referred by the Baylor Cystic Fibrosis Care Center at Texas Children`s Hospital. Login to comment
77 ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 15371908:77:403
status: NEW
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ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15371908:77:776
status: NEW
view ABCC7 p.Arg117His details
ABCC7 p.Ala455Glu
X
ABCC7 p.Ala455Glu 15371908:77:631
status: NEW
view ABCC7 p.Ala455Glu details
ABCC7 p.Trp1282*
X
ABCC7 p.Trp1282* 15371908:77:456
status: NEW
view ABCC7 p.Trp1282* details
ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 15371908:77:359
status: NEW
view ABCC7 p.Arg553* details
ABCC7 p.Arg334Trp
X
ABCC7 p.Arg334Trp 15371908:77:336
status: NEW
view ABCC7 p.Arg334Trp details
ABCC7 p.Arg347Pro
X
ABCC7 p.Arg347Pro 15371908:77:329
status: NEW
view ABCC7 p.Arg347Pro details
ABCC7 p.Gly314Glu
X
ABCC7 p.Gly314Glu 15371908:77:298
status: NEW
view ABCC7 p.Gly314Glu details
ABCC7 p.Arg347His
X
ABCC7 p.Arg347His 15371908:77:322
status: NEW
view ABCC7 p.Arg347His details
ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 15371908:77:794
status: NEW
view ABCC7 p.Asn1303Lys details
ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:77:52
status: NEW
view ABCC7 p.Gly542* details
ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:77:414
status: NEW
view ABCC7 p.Gly542* details
ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 15371908:77:373
status: NEW
view ABCC7 p.Arg1162* details
ABCC7 p.Arg352Gln
X
ABCC7 p.Arg352Gln 15371908:77:305
status: NEW
view ABCC7 p.Arg352Gln details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:77:769
status: NEW
view ABCC7 p.Ile148Thr details
ABCC7 p.Gln493*
X
ABCC7 p.Gln493* 15371908:77:668
status: NEW
view ABCC7 p.Gln493* details
ABCC7 p.Val520Phe
X
ABCC7 p.Val520Phe 15371908:77:675
status: NEW
view ABCC7 p.Val520Phe details
ABCC7 p.Ser549Arg
X
ABCC7 p.Ser549Arg 15371908:77:421
status: NEW
view ABCC7 p.Ser549Arg details
ABCC7 p.Gly85Glu
X
ABCC7 p.Gly85Glu 15371908:77:621
status: NEW
view ABCC7 p.Gly85Glu details
ABCC7 p.Ser549Asn
X
ABCC7 p.Ser549Asn 15371908:77:366
status: NEW
view ABCC7 p.Ser549Asn details
ABCC7 p.Tyr122*
X
ABCC7 p.Tyr122* 15371908:77:442
status: NEW
view ABCC7 p.Tyr122* details
ABCC7 p.Arg560Thr
X
ABCC7 p.Arg560Thr 15371908:77:396
status: NEW
view ABCC7 p.Arg560Thr details
ABCC7 p.Asp1152His
X
ABCC7 p.Asp1152His 15371908:77:484
status: NEW
view ABCC7 p.Asp1152His details
ABCC7 p.Lys710*
X
ABCC7 p.Lys710* 15371908:77:747
status: NEW
view ABCC7 p.Lys710* details
ABCC7 p.Phe508Cys
X
ABCC7 p.Phe508Cys 15371908:77:890
status: NEW
view ABCC7 p.Phe508Cys details
ABCC7 p.Ile506Val
X
ABCC7 p.Ile506Val 15371908:77:907
status: NEW
view ABCC7 p.Ile506Val details
ABCC7 p.Arg117Cys
X
ABCC7 p.Arg117Cys 15371908:77:783
status: NEW
view ABCC7 p.Arg117Cys details
ABCC7 p.Gly480Cys
X
ABCC7 p.Gly480Cys 15371908:77:661
status: NEW
view ABCC7 p.Gly480Cys details
ABCC7 p.Glu60*
X
ABCC7 p.Glu60* 15371908:77:615
status: NEW
view ABCC7 p.Glu60* details
ABCC7 p.Ile507Val
X
ABCC7 p.Ile507Val 15371908:77:900
status: NEW
view ABCC7 p.Ile507Val details
ABCC7 p.Gly178Arg
X
ABCC7 p.Gly178Arg 15371908:77:701
status: NEW
view ABCC7 p.Gly178Arg details
ABCC7 p.Ile506Met
X
ABCC7 p.Ile506Met 15371908:77:914
status: NEW
view ABCC7 p.Ile506Met details
ABCC7 p.Gly330*
X
ABCC7 p.Gly330* 15371908:77:312
status: NEW
view ABCC7 p.Gly330* details
ABCC7 p.Ala559Thr
X
ABCC7 p.Ala559Thr 15371908:77:389
status: NEW
view ABCC7 p.Ala559Thr details
ABCC7 p.Phe316Leu
X
ABCC7 p.Phe316Leu 15371908:77:754
status: NEW
view ABCC7 p.Phe316Leu details
This assay also demonstrated heterozygosity for the G542X mutation, and reflex testing for the 5T variant at CFTR intron 8 showed a genotype of 7T/9T in this patient (data not Table 3 Description of the 16 multiplex assays designed to analyze 51 CFTR mutations Multiplex Mutations Exon 1 1078delT, G314E, R352Q, G330X 7 2 R347H, R347P, R334W, 1717-1A 7, 11 3 R553X, S549N, R1162X 11, 19 4 A559T, R560T, G551D 11 5 G542X, S549R, 621ϩ1T, Y122X 4, 11 6 W1282X, 3876delA, 3905insT, D1152H 18, 20 7 3849ϩ4G, 3659delC, 1898ϩ1A 12, 19 8 405ϩ1A, 405ϩ3C, 3120A, 3120ϩ1A 3, 16 9 394delTT, E60X, G85E 3 10 A455E, ⌬F508a 9, 10 11 G480C, Q493X, V520F 10 12 711ϩ1T, G178R, 3199del6 5, 17a 13 2143delT, 2184delA, K710X, F316L 7, 13 14 I148T, R117H, R117C 4 15 N1303K, 2789ϩ5A, 3849ϩ10kbT 14b, intron19, 21 16 ⌬I507a 10 17 5Tb intron 8 a F508C and I507V, I506V, I506M variants are tested for concurrently with the ⌬F508 and ⌬I507 assays respectively. Login to comment
78 ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15371908:78:37
status: NEW
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ABCC7 p.Arg117Cys
X
ABCC7 p.Arg117Cys 15371908:78:48
status: NEW
view ABCC7 p.Arg117Cys details
b 5T reflex testing is performed for R117H- and R117C-positive individuals. Login to comment
80 ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:80:45
status: NEW
view ABCC7 p.Gly542* details
ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:80:150
status: NEW
view ABCC7 p.Gly542* details
Compound heterozygosity for the 3199del6 and G542X mutations was confirmed by parental studies, which identified 3199del6 in the patient`s mother and G542X in the father. Login to comment
84 ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:84:55
status: NEW
view ABCC7 p.Gly542* details
No definitive mutations were identified in addition to G542X and 3199del6. Login to comment
93 ABCC7 p.Ala455Glu
X
ABCC7 p.Ala455Glu 15371908:93:107
status: NEW
view ABCC7 p.Ala455Glu details
ABCC7 p.Gly314Glu
X
ABCC7 p.Gly314Glu 15371908:93:78
status: NEW
view ABCC7 p.Gly314Glu details
ABCC7 p.Ala455Val
X
ABCC7 p.Ala455Val 15371908:93:89
status: NEW
view ABCC7 p.Ala455Val details
ABCC7 p.Gly314Ala
X
ABCC7 p.Gly314Ala 15371908:93:60
status: NEW
view ABCC7 p.Gly314Ala details
Two previously unreported missense alleles were identified: G314A (allelic to G314E) and A455V (allelic to A455E). Login to comment
94 ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 15371908:94:56
status: NEW
view ABCC7 p.Arg553* details
ABCC7 p.Arg553Gly
X
ABCC7 p.Arg553Gly 15371908:94:17
status: NEW
view ABCC7 p.Arg553Gly details
In addition, the R553G mutation which is allelic to the R553X, was identified in one patient (data not shown). Login to comment
103 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:103:75
status: NEW
view ABCC7 p.Ile148Thr details
Among unaffected individuals who tested positive on carrier screening, the I148T allele was found in approximately 9.2% of carriers (16/173), compared to Ϸ6.4% from the previously cited study8 (P ϭ 0.21). Login to comment
104 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:104:131
status: NEW
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In contrast to carrier screening results, none of the 155 diagnostic cases tested by MALDI-TOF mass spectrometry were positive for I148T. Login to comment
105 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:105:59
status: NEW
view ABCC7 p.Ile148Thr details
This finding is consistent with the significantly elevated I148T frequency in carrier screens versus diagnostic cases,8,9 and the relatively small number of diagnostic tests in our study. Login to comment
106 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:106:52
status: NEW
view ABCC7 p.Ile148Thr details
This observed difference in frequency suggests that I148T is a benign variant, and that 3199del6 could instead represent the actual mutation. Login to comment
107 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:107:126
status: NEW
view ABCC7 p.Ile148Thr details
Up until now, limited data had been available for 3199del6 because systematic analysis was largely based on reflex testing of I148T-positive samples. Login to comment
109 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:109:62
status: NEW
view ABCC7 p.Ile148Thr details
In contrast, our assay tests for 3199del6 simultaneously with I148T in an extended panel for CF. Login to comment
111 ABCC7 p.Gly178Arg
X
ABCC7 p.Gly178Arg 15371908:111:147
status: NEW
view ABCC7 p.Gly178Arg details
The mass spectrometry chromatogram indicates the expected wild-type and mutant peaks for each mutation in the multiplex CF assay shown (31999del6, G178R, 711ϩ1T). Login to comment
113 ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15371908:113:73
status: NEW
view ABCC7 p.Gly542* details
ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:113:156
status: NEW
view ABCC7 p.Ile148Thr details
The identification of a CF patient with a compound heterozygous 3199del6/G542X genotype represents the first report of 3199del6 that is not associated with I148T on a CF chromosome. Login to comment
114 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:114:97
status: NEW
view ABCC7 p.Ile148Thr details
This indicates that 3199del6 is a disease-causing mutation that can occur on a haplotype without I148T. Login to comment
116 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:116:149
status: NEW
view ABCC7 p.Ile148Thr details
In addition to our Hispanic CF patient, we identified an asymptomatic Caucasian individual who tested positive on carrier screening for 3199del6 and I148T (phase unknown). Login to comment
119 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:119:64
status: NEW
view ABCC7 p.Ile148Thr details
Our results provide additional support to the interpretation of I148T as a benign variant, although its interaction with the 3199del6 mutation is not fully delineated. Login to comment
120 ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 15371908:120:55
status: NEW
view ABCC7 p.Ile148Thr details
These findings provide additional support for removing I148T from the ACMG recommended carrier screening panel for CF. Login to comment