ABCMdb

PMID: 21474639

Rohlfs EM, Zhou Z, Heim RA, Nagan N, Rosenblum LS, Flynn K, Scholl T, Akmaev VR, Sirko-Osadsa DA, Allitto BA, Sugarman EA
Cystic fibrosis carrier testing in an ethnically diverse US population.
Clin Chem. 2011 Jun;57(6):841-8. Epub 2011 Apr 7., [PubMed]

Sentences

No. Mutations Sentence Comment

21 ABCC7 p.Tyr1092* For example, c.3744delA accounts for 2.2%-5.7% of CF chromosomes in Hispanics (11, 16, 17), and p.Y1092X accounts for 37.5% of CF chromosomes in Iraqi Jews (18). Login to comment 61 ABCC7 p.Phe508Cys ABCC7 p.Ile506Val ABCC7 p.Ile507Val The mutation analysis discriminated between p.F508del and the benign polymorphisms p.F508C, p.I506V, and p.I507V. Login to comment 65 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Leu206Trp ABCC7 p.Asp1152His The median fluorescent intensity was determined, and the presence or absence of mutant and wild-type alleles was evaluated from the ratio of the mutant signal to the wild-type signal for the following mutations: c.1155_1156dupTA, c.2657ϩ5GϾA, c.3717ϩ12191CϾT, p.A455E, p.D1152H, p.F508del, p.G542X, p.G551D, p.I507del, p.L206W, p.N1303K, p.R117H, p.W1282X, and c.54-5940_ 273ϩ10250del21kb. Login to comment 73 ABCC7 p.Arg117His CFTR intron 8 poly(T) variant analysis was performed for all samples positive for p.R117H. Login to comment 91 ABCC7 p.Arg117His p.F508del accounted for 57.7% of all mutations, followed by p.R117H (8.9%). Login to comment 92 ABCC7 p.Arg117His ABCC7 p.Arg117His Of the 841 individuals who carried a single p.R117H mutation, 3 females carried 2 copies of the 5T allele, whereas the majority (n ϭ 757) did not carry a 5T allele in cis with the p.R117H mutation on the basis of the poly(T) results of 7T/7T, 7T/9T, or 7T/11T. Login to comment 93 ABCC7 p.Arg117His The poly(T) background of the p.R117H mutation could not be determined for the remaining 81 individuals who carried 5T/7T or 5T/9T. Login to comment 95 ABCC7 p.Arg117His Twenty-one of these individuals carried at least 1 copy of p.R117H (Table 1). Login to comment 96 ABCC7 p.Arg117His Twenty of the 21 individuals carried either 7T/7T or 7T/9T, and 1 individual, a 32-year-old woman, carried 5T/9T and p.R117H/ p.F508del. Login to comment 98 ABCC7 p.Arg117His ABCC7 p.Arg347Pro Of these mutations, p.R117H, c.3717ϩ 12191CϾT, and p.R347P are included in the ACMG panel, a finding consistent with that panel`s inclusion of mutations associated with mild or severe disease (19). Login to comment 102 ABCC7 p.Arg764* Four of the newly added mutations were identified in African Americans, and of these mutations, p.R764X accounted for 0.63% of all mutations detected in this group. Login to comment 116 ABCC7 p.Ile148Thr For example, although p.I148T was initially identified in Ͼ0.1% of affected patients, it was subsequently reclassified as a benign allele after a frequency higher than expected was observed in the carrier-screening population (29, 30). Login to comment 118 ABCC7 p.Ile148Thr When the observed Caucasian carrier frequency was corrected with the detection rate of 91.56% [Table 1, Cystic Fibrosis Foundation data excluding p.I148T, in (10)], the carrier frequency in Caucasians increased from 1 in 28 to 1 in 25. Login to comment 123 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Gly542* ABCC7 p.Arg352Gln ABCC7 p.Leu206Trp ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Arg117Cys CFTR mutationsa Individuals, n p.F508del/p.R117H 16 5T/9T 1 7T/9T 15 p.F508del/p.D1152H 3 p.R117H/p.R117H, 7T/7T 2 p.D1152H/p.D1152H 2 p.W1282X/p.D1152H 2 p.D1152H/p.G551D 1 c.3717ϩ12191CϾT/p.R352Q 1 c.3717ϩ12191CϾT/c.3717ϩ12191CϾT 1 p.F508del/c.3717ϩ12191CϾT 1 p.F508del/p.L206W 1 p.F508del/p.R117C 1 p.F508del/p.R347H 1 p.F508del/p.R347P 1 p.R117H/p.W1282X, 7T/7T 1 p.R117H/p.G551D, 7T/7T 1 p.R117H/p.G542X, 7T/9T 1 a Human Genome Variation Society nomenclature [Ogino et al. (23)]. Login to comment 127 ABCC7 p.Ser549Arg ABCC7 p.Asp1152His ABCC7 p.Trp1089* Eighteen different mutations were identified in Ashkenazi Jewish individuals; 5 non-ACMG mutations (p.D1152H, c.54-5940_273ϩ10250del21kb, p.S549R, p.W1089X, p. Login to comment 128 ABCC7 p.Gln359Lys [Q359K;T360K]) accounted for 13% of all alleles detected in this group. Login to comment 131 ABCC7 p.Pro574His ABCC7 p.Thr338Ile ABCC7 p.Met1101Lys ABCC7 p.Ser1255* ABCC7 p.Lys710* ABCC7 p.Gln890* ABCC7 p.Gly178Arg ABCC7 p.Gln1238* ABCC7 p.Ser364Pro ABCC7 p.Gly330* Four mutations (p.S1255X, p.G330X, c.313delA, p.S364P) were identified only in African Americans, 8 mutations (p.G178R, p.T338I, c.262_ 263delTT, p.M1101K, c.442delA, p.K710X, p.P574H, p.Q1238X)wereidentifiedonlyinCaucasians,and3mu- tations (c.580-1GϾT, c.531delT, p.Q890X) were identified only in Hispanics. Login to comment 132 ABCC7 p.Tyr1092* Consistent with the literature, an apparently ethnicity-limited mutation (p.Y1092X CϾG) was found in 2 Jewish individuals (18). Login to comment 140 ABCC7 p.Arg75* Three mutations (c.54-5940_273ϩ10250del21kb, c.2052dupA, and p.R75X) Table 2. Login to comment 148 ABCC7 p.Arg75* ABCC7 p.Arg709* An additional 3 mutations (c.803delA, p.R75X, and p.R709X) identified in Asians accounted for 8.6% of all alleles detected in this population. Login to comment 152 ABCC7 p.Arg117His Ninety-four percent of the p.R117H-positive individuals with a second mutation did not carry a 5T allele. Login to comment 153 ABCC7 p.Arg117His ABCC7 p.Arg117His p.R117H in cis with 5T generally confers moderate to severe CF, whereas p.R117H in cis with 7T may confer a mild form of CF, a later CF onset, CBAVD, or no apparent disease (35-37). Login to comment 160 ABCC7 p.Ser1255* In addition, some mutations (such as p.S1255X, which accounted for Ͼ1% of the mutations identified in African Americans) appear to be limited to certain ethnic groups. Login to comment 176 ABCC7 p.Arg117His Additionally, in contrast to our analysis, Strom et al. do not include carriers of R117H plus 7T in their analysis, thereby lowering their overall carrier frequency. Login to comment