PMID: 11388756

Heim RA, Sugarman EA, Allitto BA
Improved detection of cystic fibrosis mutations in the heterogeneous U.S. population using an expanded, pan-ethnic mutation panel.
Genet Med. 2001 May-Jun;3(3):168-76., [PubMed]
Sentences
No. Mutations Sentence Comment
55 ABCC7 p.Phe508Cys
X
ABCC7 p.Phe508Cys 11388756:55:78
status: NEW
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The 70-mutation assay distinguished between the ⌬F508 mutation and the F508C sequence variant. Login to comment
56 ABCC7 p.Phe508Cys
X
ABCC7 p.Phe508Cys 11388756:56:58
status: NEW
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ABCC7 p.Ile506Val
X
ABCC7 p.Ile506Val 11388756:56:65
status: NEW
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ABCC7 p.Ile507Val
X
ABCC7 p.Ile507Val 11388756:56:83
status: NEW
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ABCC7 p.Ile506Met
X
ABCC7 p.Ile506Met 11388756:56:72
status: NEW
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The 86-mutation assay distinguished ⌬F508 from the F508C, I506V, I506M, and I507V sequence variants. Login to comment
83 ABCC7 p.Trp1316*
X
ABCC7 p.Trp1316* 11388756:83:77
status: NEW
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ABCC7 p.Tyr122*
X
ABCC7 p.Tyr122* 11388756:83:17
status: NEW
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ABCC7 p.Trp1310*
X
ABCC7 p.Trp1310* 11388756:83:65
status: NEW
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These mutations, Y122X, 556delA, 2909delT, 3358delAC, 3750delAG, W1310X, and W1316X, were subsequently excluded from the 86-mutation panel. Login to comment
85 ABCC7 p.Pro574His
X
ABCC7 p.Pro574His 11388756:85:40
status: NEW
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ABCC7 p.Tyr563Asp
X
ABCC7 p.Tyr563Asp 11388756:85:33
status: NEW
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ABCC7 p.Gln1238*
X
ABCC7 p.Gln1238* 11388756:85:77
status: NEW
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ABCC7 p.Cys524*
X
ABCC7 p.Cys524* 11388756:85:26
status: NEW
view ABCC7 p.Cys524* details
These mutations, 574delA, C524X, Y563D, P574H, 2043delG, 3662delA, 3821delT, Q1238X, and 3849 ϩ 4AϾG, as well as the previous seven mutations, make no detectable contribution to mutation detection in the general U.S. CF population. Login to comment
87 ABCC7 p.Ser1251Asn
X
ABCC7 p.Ser1251Asn 11388756:87:148
status: NEW
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ABCC7 p.Thr338Ile
X
ABCC7 p.Thr338Ile 11388756:87:41
status: NEW
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ABCC7 p.Ser549Ile
X
ABCC7 p.Ser549Ile 11388756:87:98
status: NEW
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ABCC7 p.Gln552*
X
ABCC7 p.Gln552* 11388756:87:105
status: NEW
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ABCC7 p.Arg1283Met
X
ABCC7 p.Arg1283Met 11388756:87:160
status: NEW
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ABCC7 p.Gly91Arg
X
ABCC7 p.Gly91Arg 11388756:87:11
status: NEW
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ABCC7 p.Thr360Lys
X
ABCC7 p.Thr360Lys 11388756:87:70
status: NEW
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ABCC7 p.Gln359Lys
X
ABCC7 p.Gln359Lys 11388756:87:64
status: NEW
view ABCC7 p.Gln359Lys details
These were G91R, 711 ϩ 5GϾA, T338I, 712-1GϾT, Q359K/T360K, 1161delC, 1609delCA, S549I, Q552X, 1949del84, 1989 ϩ 5GϾT, S1251N, and R1283M. Login to comment
105 ABCC7 p.Thr338Ile
X
ABCC7 p.Thr338Ile 11388756:105:139
status: NEW
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Examples include 394delTT (identified in only two U.S. Caucasian alleles, although it has a frequency of 1.1-28.8% in Northern Eu- rope5), T338I (not identified in the United States, although it has a frequency of 9.9% in Sardinia and nearly 0.1% in Italy5), and 1609delCA (not identified in 434 Southern or mixed European Caucasian alleles and 74 Hispanic alleles, although it has a frequency of 4.1% in the east of Spain5). Login to comment
107 ABCC7 p.Met1101Lys
X
ABCC7 p.Met1101Lys 11388756:107:17
status: NEW
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Examples include M1101K (identified in 6/1,216 Caucasian alleles including one of Southern European origin, but originally described as specific to the Hutterite population15), and 3120 ϩ 1GϾA (identified in 4/4,634 Caucasian alleles, but reported to be specific to African Americans6). Login to comment
109 ABCC7 p.Trp1282*
X
ABCC7 p.Trp1282* 11388756:109:118
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 11388756:109:126
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 11388756:109:111
status: NEW
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More strikingly, the five mutations reported to account for 97% of Ashkenazi Jewish chromosomes (⌬F508, G542X, W1282X, N1303K, and 3849 ϩ 10 kbCϾT)16 accounted for only 39/48 chromosomes in this study (81.3%). Login to comment
110 ABCC7 p.Ala455Glu
X
ABCC7 p.Ala455Glu 11388756:110:298
status: NEW
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ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 11388756:110:305
status: NEW
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ABCC7 p.Asp1152His
X
ABCC7 p.Asp1152His 11388756:110:316
status: NEW
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This difference is unlikely to be due to ascertainment, since the observed frequency of ⌬F508 (29%) is equivalent to the frequency of 30% reported by Abeliovich et al.16 In this study, the detection of an additional three mutations was required to bring the overall detection rate to 95.4% (A455E, R553X, and D1152H). Login to comment
116 ABCC7 p.Trp1089*
X
ABCC7 p.Trp1089* 11388756:116:12
status: NEW
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Of the two, W1089X is relatively frequent (1.2%) but was originally reported in one Turkish and one Egyptian Jewish individual17 and had not been described in Hispanics until now. The other, 1078delT,18 was identified on one Hispanic chromosome and no others. Login to comment
118 ABCC7 p.Tyr1092*
X
ABCC7 p.Tyr1092* 11388756:118:181
status: NEW
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Examples include 711 ϩ 1GϾT (frequency of 6.9% in Tunisia5 and 9% in Quebec19), 1677delTA (originally described in a small Georgian ethnic group in the U.S.S.R.20), and Y1092X (originally identified in the Canadian population21 and in the homozygous state in a CF patient of Jewish Egyptian origin3). Login to comment
119 ABCC7 p.Trp1089*
X
ABCC7 p.Trp1089* 11388756:119:22
status: NEW
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With the exception of W1089X, 1078delT, and 2869insG, all other mutations identified in Hispanics were also identified in Caucasians. Login to comment
124 ABCC7 p.Tyr563Asp
X
ABCC7 p.Tyr563Asp 11388756:124:295
status: NEW
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ABCC7 p.Ser364Pro
X
ABCC7 p.Ser364Pro 11388756:124:288
status: NEW
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As expected, after ⌬F508 the most common African American mutation was 3120 ϩ 1GϾA, with a frequency (13.8%) comparable to that reported by Macek et al. (12.3%).6 Five mutations that are considered to be African American specific (405 ϩ 3AϾC, ⌬F311, S364P, Y563D, and 3662delA)6,12,22 were not observed in any African Americans included in this study, however. Login to comment
125 ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 11388756:125:136
status: NEW
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ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 11388756:125:129
status: NEW
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ABCC7 p.Arg1158*
X
ABCC7 p.Arg1158* 11388756:125:121
status: NEW
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ABCC7 p.Arg1066Cys
X
ABCC7 p.Arg1066Cys 11388756:125:189
status: NEW
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It was unexpected that six of the next most common mutations after 3120 ϩ 1GϾA would be of Caucasian origin (R1158X, R117H, G551D, 1812-1GϾA, 1898 ϩ 1GϾA, and R1066C). Login to comment
126 ABCC7 p.Arg1158*
X
ABCC7 p.Arg1158* 11388756:126:135
status: NEW
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ABCC7 p.Arg1158*
X
ABCC7 p.Arg1158* 11388756:126:213
status: NEW
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ABCC7 p.Arg1066Cys
X
ABCC7 p.Arg1066Cys 11388756:126:10
status: NEW
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Of these, R1066C has a frequency of 3.1% in Portugal,5 1812-1GϾA was originally identified in 1/50 Spanish CF chromosomes,24 and R1158X was originally identified in an Italian CF patient.13 Our detection of R1158X on four African American chromosomes (2.0%) was not anticipated. Login to comment
127 ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 11388756:127:238
status: NEW
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ABCC7 p.Ser1255*
X
ABCC7 p.Ser1255* 11388756:127:301
status: NEW
view ABCC7 p.Ser1255* details
ABCC7 p.Gly480Cys
X
ABCC7 p.Gly480Cys 11388756:127:231
status: NEW
view ABCC7 p.Gly480Cys details
ABCC7 p.Gly330*
X
ABCC7 p.Gly330* 11388756:127:224
status: NEW
view ABCC7 p.Gly330* details
ABCC7 p.Ala559Thr
X
ABCC7 p.Ala559Thr 11388756:127:245
status: NEW
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Of the 20 mutations that account for the overall detection rate in African Americans when ⌬F508 is excluded, nine that account for 23.6% of the chromosomes analyzed are considered to be "African" mutations6 (444delA, G330X, G480C, R553X, A559T, 2307insA, 3120 ϩ 1GϾA, 3791delC, and S1255X). Login to comment
128 ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 11388756:128:338
status: NEW
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ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 11388756:128:293
status: NEW
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ABCC7 p.Arg334Trp
X
ABCC7 p.Arg334Trp 11388756:128:324
status: NEW
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ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 11388756:128:403
status: NEW
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ABCC7 p.Gln493*
X
ABCC7 p.Gln493* 11388756:128:331
status: NEW
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ABCC7 p.Arg1158*
X
ABCC7 p.Arg1158* 11388756:128:395
status: NEW
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ABCC7 p.Arg1066Cys
X
ABCC7 p.Arg1066Cys 11388756:128:387
status: NEW
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By comparison, eight "African" mutations accounted for a similar percentage of the chromosomes analyzed (23%) in the study by Macek et al.6 In contrast, 11 of the 20 mutations detected in this study are considered to be "Caucasian" mutations and account for 10.5% of the chromosomes analyzed (R117H, 621 ϩ 1GϾT, R334W, Q493X, G551D, 1812-1GϾA, 1898 ϩ 1GϾA, R1066C, R1158X, R1162X, and 3905insT). Login to comment
133 ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 11388756:133:22
status: NEW
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We did not detect the R1162X mutation, although it has a carrier frequency of 6.7% among Zuni Native Americans.25 Despite its small size, our sample set is the largest reported to date. Login to comment