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Figure 1 | BMC Medical Genetics

Figure 1

From: Large genomic rearrangements in the CFTRgene contribute to CBAVD

Figure 1

A) Confirmation of complex deletion c.54-5811_c.164+2186del8108ins182 [ CFTR dele2] in CBAVD. Rearrangement c.54-5811_c.164+2186del8108ins182 (upper panel) consists of a gross deletion of 8108 bp spanning exon 2 (dotted area) and an insertion of 182 bp (grey area) at the deletion junction between the nucleotide 54-5811 of intron 1 (IVS1 nt 18294) and the nucleotide 164+2186 of intron 2 (IVS2 nt 2186) [according to the recommended international nomenclature with the A of the ATG start codon numbered as +1]. The 182-bp insertion is part of intron 3 between IVS3 nucleotides 6780 and 6961 but in inverted orientation (arrow). This complex in/del is also termed c.186-5811_c.296+2186del8108+ins182 with the A of the ATG translation start codon numbered as +133 in accordance with the GenBank reference sequence for the CFTR gene on chromosome 7 (NM_000492.2) and the CF mutation database [4]. It was recently reported as IVS1-5811_IVS2+2186del8108ins182 in one patient with cystic fibrosis [27]. A specifically-designed junction fragment amplification test (lower panel) confirmed the presence of the heterozygous deletion, indicated by specific PCR products on 2% agarose gels (left) by comparison with the non deleted allele. The deletion breakpoint junctions (indicated by vertical bars) and inserted sequences were determined by direct sequencing (right). B) Confirmation of complex deletion c.3964-3890_c.4443+3143del9454ins5 [ CFTRdele22_24 or CFTR dele25_27] in CBAVD. Rearrangement c.3964-3890_c.4443+3143del9454ins5 (upper panel) consists of a gross deletion of 9454 bp (dotted area) encompassing exons 25 to 27 [22 to 24], the stop codon and the poly(A) signal. A small insertion of 5 bases (TAACT) was observed at the junction but is too small to allow any determination of its origin (arrow). The same rearrangement has recently been described in one patient with cystic fibrosis as c.4096-3890_c.4575+3143del9454ins5 with the A of the ATG translation start codon numbered as +133 in accordance with the GenBank reference sequence for the CFTR gene on chromosome 7 (NM_000492.2) or as IVS21-3890Stop+3143del9454insTAACT [15]. A specifically-designed junction fragment amplification test (lower panel) confirmed the presence of the heterozygous deletion, indicated by specific PCR products on 2% agarose gels (left) by comparison with the non deleted allele. The deletion breakpoint junctions (indicated by vertical bars) and inserted sequences were determined by direct sequencing (right).

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