ABCMdb

PMID: 22137130

Cordovado SK, Hendrix M, Greene CN, Mochal S, Earley MC, Farrell PM, Kharrazi M, Hannon WH, Mueller PW
CFTR mutation analysis and haplotype associations in CF patients.
Mol Genet Metab. 2012 Feb;105(2):249-54. doi: 10.1016/j.ymgme.2011.10.013. Epub 2011 Oct 26., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Chromosomes containing the F508del (p.Phe508del), G542X (p.Gly542X) and N1303K (p.Asn1303Lys) mutations shared a common haplotype subgroup, consistent with a common ancient European founder. Login to comment 34 ABCC7 p.Asn1303Lys Four N1303K DBS specimens were provided by the California Department of Public Health NBS Program; two from patients diagnosed with CF and two from patients diagnosed with CF-related metabolic syndrome [15]. Login to comment 79 ABCC7 p.Ile1027Thr The I1027T mutation, the third mutation in two specimens, has been found in cis with the F508del mutation greater than 5% in the Brittany population (western France) [19]. Login to comment 89 ABCC7 p.Leu467Pro In four samples, 2184delA/ 394delTT, 3905insT/1248+1G→A, 3120+ 1G→A/-102T→A and 3120+1G→A/L467P, the predicted haplotype could not be unambiguously assigned to one of the two CF-causing mutations. Login to comment 101 ABCC7 p.Trp1282* ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Ile1027Thr ABCC7 p.Ile1027Thr CFTR mutation 1 Gene location CFTR mutation 2 Gene location CFTR mutation 3 Gene location S549N Ex12 3120+1G→A Intron 18 -102T→A Promoter F508del Ex11 G542X Ex12 185+4A→T Intron1 F508del Ex11 F508del Ex11 I1027T Ex19 F508del Ex11 W1282X Ex23 I1027T Ex19 only by the number of repeats of the IVS8CA microsatellite; 32 chromosomes contained 17 repeats and 29 chromosomes contained 23 repeats. Login to comment 102 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The F508del haplotype that contained 23 repeats of the IVS8CA microsatellite was identical to the predicted haplotypes associated with G542X (N=6 of 6), N1303K (N=6 of 6), del Ex17a, b and 18 (N=1 of 1), and 3849+10 kb C→T (N=1 of 2). Login to comment 104 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Arg1066Cys ABCC7 p.Gln39* ABCC7 p.Phe508Cys ABCC7 p.Arg1066His Mutation N alleles c.966T>G(5'flanking) c.234T>A(5'flanking)a c.-8G>C(5'UTR) c.-4G>C(Exon1) c.274-179G>A(Intron3) c.743+40A>G(Intron6) c.744-31TTGA(5_7)(Intron6) c.869+11C>T(Intron7) c.869+88T>A(Intron7) c.1209+43T>G(Intron9) IVS8CA(15-23)(Intron9) TG(10-13)_T(5-9)(Intron9) c.1393-61A>G(Intron10) M470V(Exon11) F508del(Exon11) c.1766+152T>A(Intron13) c.1767-231T>C(Intron13) c.1767-136T>C(Intron13) c.1767-132A>G(Intron13) c.2562T>G(Exon15) c.2604A>G(Exon15) c.2619+86_2619+87del(Intron15) c.2619+106T>A(Intron15) c.2909-92G>A(Intron17) IVS17bCA(11-17)(Intron20) c.3368-140A>C(Intron20) c.3469-65C>A(Intron21) F508del 32 TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- GA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- A5- 55- 55- 55- 66- 66- 66- 66- 66- 66- 66- 66- 66- 66- 55- 55- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TC- TT- TT- TT- TC- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TG- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- T17- 10_9- G- F508del- TA- 13C F508del 29 G23- 10_9- G- F508del- TA- 13C F508del 1 G21- 10_9- G- GG- G-F508del- TA- 13C F508del 1 G17- 10_9- G- F508del- A- G- delTA- 17- C- A N1303K 6 G542X 6 3849+10kbC→T 1 del Ex17a, b, Ex18 1 GG- GG- GG- 23- 10_9- GG-F508- T- TA- 13- C A455E 1 G22- 10_9- G- F508- T- TA- 13- C 621+1G→T 5 G21- 10_9- G- GG- GG- F508C- TA- 13- C 711+1G→T 3 3272-26A→G 2 3659delC 2 R347P 2 G16- 11_7- A- A-F508- TA- 13C del Ex 2, 3 2 del Ex 17a,17b 2 Normal 1 R334W 2 G17- 11_7- A- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA-AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- A-AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- AA- F508- TA- 13C 2183AA→G 2 G16- 10_7- F508- TATA- TATA- TATA- TATA- TATA- TATA- 13C del Ex 2 1 G16- 11_7- F508- 14C 1288insTA 1 G16- 12_7- F508- 13C Normal 1 G16- 12_7- F508- 13C R1162X 1 G17- 10_7- F508- 13C del Ex 2,3 1 G16- 11_7- F508- A17- C del Ex 17a,17b 1 GA- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT- TT-16- 11_7- F508- 14- C G85E 1 G16- 11_7- F508- 15C 1898+1G→A 1 G16- 11_7- F508- G13- C no mut detected 1 GT- TT- T16- 10_7- F508- 13C no mut detected 1 G16- 10_7- F508- 17A W1282X 2 G17- 10_7- F508- 17A W1282X 4 GC- CC- C17- 10_7- F508- delTA- 17- A Q39X 1 I507del 1 3849+10kbC→T 1 R560T 2 1717-1G→A 2 G551D 3 G16- 10_7- F508- delTA- 17- A G551D 2 1154insTC 1 G16- 10_7- F508- delTA- 17- 1717- 17A 1717-1G→A 1 2789+5G→A 1 GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- G17- 10_7- F508- AdelTA- A R1066C 1 GG- 17- 10_7- F508- delTA- A R1066H 1 GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- GG- G17- 9_7- F508- delTAC R553X 3 GG- GG- CA- AA- AA- AA- A17- 12_7- F508- delTA- 11- C 3121-1G→A 1 C17- 12_7- F508- delTA- 11- C R334W 1 G17- 12_7- F508- TA- 13- C (TG)13T5b 1 G17- 13_5- F508- delTA- 13- C CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- CC- R117H 1 CA- 6C- TT- 15- 12_5- AG- F508- T- TT- AT- ATA- TG- 13A- C R117H1 1 CA- 6C- TT- 16- 12_5- AG- F508- T- TT- AT- ATA- TG- 13A- C 1717-1G→A 1 R117Hb 1 GA- 6C- TT- 16- 10_7- AA- F508- A- TC- AG- AdelTA- TG- 13A- C 144c a Variation found in a sample where the haplotype could not be predicted. Login to comment 109 ABCC7 p.Arg117His ABCC7 p.Arg117His Molecular analysis of the R117H mutation The R117H mutation, known to be variable in its disease expression, was found in three specimens. Login to comment 111 ABCC7 p.Arg117His ABCC7 p.Arg117His The third R117H predicted haplotype contained a 7T variant and multiple differences from the other two R117H haplotypes. Login to comment 112 ABCC7 p.Arg117His The haplotype containing the R117H mutation with the 7T variant was identical to the 1717-1G→A containing haplotype; however the significance is unknown since each is only found in one chromosome (Table 3). Login to comment 113 ABCC7 p.Arg117His ABCC7 p.Arg117His A single CF-related metabolic syndrome chromosome containing the 5T variant in the absence of R117H had a unique haplotype quite different from all other R117H containing haplotypes. Login to comment 118 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Half (N=77) of the 152 chromosomes examined shared a common haplotype subgroup which was associated with three of the most prevalent CF-causing mutations, F508del, G542X, and N1303K. Login to comment 119 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* To understand CFTR mutations, a previous study assessing the origin of 27,177 CF chromosomes from 29 European countries and three North African countries described the five most common CF-causing mutations: F508del (66.8%), G542X (2.6%), N1303K (1.6%), G551D (1.5%) and W1282X (1.0%) [22]. Login to comment 120 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Similarly, Bobadilla et al. described the five most common CF-causing mutations in the U.S., which included F508del (68.6%), G542X (2.4%), G551D (2.1%), W1282X (1.4%) and N1303K (1.3%) [23]. Login to comment 121 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Hence, F508del, G542X, and N1303K are the more common mutations in Caucasians from Europe and the United States. Login to comment 123 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The haplotypes identified in the present study were consistent with the Spanish patient findings, showing that F508del, G542X, and N1303K again share a common haplotype subgroup [24]. Login to comment 124 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Of our 62 F508del containing chromosomes (excluding the one probable recombinant), 29 predicted haplotypes are identical across 27 polymorphisms from the promoter to intron 21 to the G542X containing haplotypes (N=6) and the N1303K containing haplotypes (N=6). Login to comment 138 ABCC7 p.Arg117His ABCC7 p.Ser1251Asn ABCC7 p.Phe508Cys Researchers found that the phenotypic severity of a CF-causing mutation could be impacted by the genomic context of the CFTR gene as seen when R117H is in cis with the 5T variant and when S1251N is in cis with F508C [33,34]. Login to comment 140 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* For example, when a newborn specimen is positive for R117H and either F508del, G542X or N1303K, and also carries both an 5T and a 9T variant, a clinician could use haplotype information to proceed with a strong probability that the 9T variant is in cis with F508del, G542X or N1310K and not R117H (Table 3). Login to comment 141 ABCC7 p.Arg117His This study also shows that R117H may reside on the opposite chromosome from nearly all of the listed mutations in Table 3 because it has a different polymorphism background. Login to comment