Molecular characterisation of the CFTR rearrangements
| Patient no. | Rearrangement | Simplified name | Exon(s) involved | Linked haplotype IVS1(CA)-IVS8(CA)- IVS17b(TA)-IVS17b(CA) | Motif sequence at the breakpoints |
|---|---|---|---|---|---|
| The nomenclature recommendations were followed (www.hgvs.org) but the A of the ATG translation start codon was numbered as +133, according to the current CFTR gene numbering (GenBank NM_000492.2) and the CF mutation database. The new rearrangements are indicated in bold. | |||||
| *The same indel was described in a CF patient with paternal isodisomy22 and further found in a French CF patient.14 | |||||
| †The same CFTRdele2 as that described by Mekus and Tümmler (www.genet.sickkids.on.ca/cftr) was identified using specific primers provided by T Dörk. | |||||
| ‡Abnormal segregation of the IVS17b(TA) microsatellite was observed using the flanking primers,42 as the 3′ breakpoint is located within this site. The number of (TA) repeats, indicated in italics, has thus been determined by sequencing. | |||||
| §The linked haplotype was demonstrated in case nos. 5 and 6 and hypothesised in case nos. 7 and 8. | |||||
| ¶The precise IVS1(CA) allele could not be determined, as the father’s DNA was not available. | |||||
| **The linked haplotype was hypothesised, considering the most frequent haplotype IVS8(CA)23-IVS17b(TA)33-IVS17b(CA)13 linked to G542X.43 | |||||
| 1 | c.136_c.185+69del119bpins299bp* | 136del119ins299 | Part of 1 (codons 2–18) | 23–16–29–13 | Inverted CCATG |
| 2 | c.186−?_c.296+?del† | CFTRdele2 | 2 | 24–16–30–14 | ND |
| 3 | c.3413_c.3499+268del355bpins TGTTAA | 3413del355ins6 | Part of 17b (codons1094–1122) | 23–16–del–13 | Direct CTGT andAT rich |
| 4 | c.2752–674_c.3499+198del9855bp | CFTR dele14b–17b | 14b–17b | 23–16–13–13‡ | Direct TCGG andAT rich |
| 5–8 | c.3121–977_c.3499+248del2515bp | CFTR dele17a–17b | 17a–17b | 23–16–7–13‡,§ | Symmetric ATG andAT rich |
| 9 | [c.297−?_c.1716+?del; c.2752−?_c.3120+?del] | CFTR dele3–10,14b–16 | 3–10 and 14b–16 | 22 or 23–16–7–17¶ | ND |
| 10 | CFTRdele1–24 | CFTR dele1–24 | 1–24 | del–del–del–del | ND |
| 11 | c.406−?_c.1341+?dup | CFTR dup4–8 | 4–8 | 27–17–7–17** | ND |