Five splicing, one frameshift, and one missense mutations in CHRNE in the five patients
| No. | Mutation | Position on genomic DNA | Splicing consequence | |||
|---|---|---|---|---|---|---|
| *Homozygous mutation. †Characterised using transfected COS cells. ‡Characterised using muscle mRNA. NA, not applicable. §We previously reported that P245L is a low expressor mutation that also prolongs channel opening events two fold.18 | ||||||
| 1 | g.IVS6-1G→C* | 3′ splice site of intron 6 | Active cryptic 3′ splice site† | |||
| 2 | g.IVS9-1G→A* | 3′ splice site of intron 9 | Retention of intron 9† | |||
| Skipping of exon 10† | ||||||
| 3 | g.IVS10-9_c.1167dup16* | 16 bp duplication comprising 8 bp at 3′ end of intron 10 and 8 bp at 5′ end of exon 11 | Silencing of downstream 3′ splice site† | |||
| 4 | c.1259_g.IVS11+15del23 | 23 bp deletion comprising 8 bp at 3′ end of exon 11 and 15 bp at 5′ end of intron 11 | Retention of intron 11‡ | |||
| c.1033delG | exon 10 (61st nucleotide) | NA | ||||
| 5 | c.857G→T (p.R286M) | G→T substitution at 3′ end of exon 8 | Skipping of exon 8† | |||
| c.734C→T (p.P245L§) | exon 7 (193rd nucleotide) | NA | ||||