normal ...CAG insertion GGA GGT ... GGA AAC TTT GCT ...

mutant ...CAG gta...taa... cag GGA deletion AAC TTT GCT ...

exon 6 exon 8intron 5 exon 6exon 5 intron 5

normal ... GGT GAA AAA GGT ... GGA AAC TTT GCT ...

mutant ... GGT GAA AAA GTG ...TGG A AC TTT GCT ... GTA ATG

5 7 84exon numberAC

6

exon 6 exon 7

c.430-1G>C

Supplementary Figure 1 – cDNA analysis reveals that three splice site alterations generate multiple RNA isoforms. (A) c.430-1G>C (IVS 6) results in 3 different isoforms: (1) retention of intron 5 and skipping of exon 7; (2) skipping of exon 7; (3) deletion of one nucleotide at the acceptor splice of exon 7 resulting in a frameshift. (B) c.3003+5G>A (IVS 43) results in 2 different isoforms: (1) skipping of exon 43; (2) aberrant splicing due to cryptic splice site in exon 43 with frameshift as a consequence. (C) c.4074+1G>T (IVS 52) results in 2 different isoforms: (1) skipping of exon 52 and part of exons 51 and 53; (2) aberrant splicing due to cryptic splice site in exon 52 with frameshift.

(A) 1 & 2

(A) 3

c.3003+5G>A 41 42 43

GTGAA44

normal ... GGT CCC TCT GGT GCC GAA ... GGT GAG CCC...

mutant ... GGT CCC TCT deletion GGT GAG CCC ...

exon 42 exon 43 exon 44

normal ... CGT GGT GAG AGA GGA TTC CCT GGC TTG CCT GGC CCA TCG GGT GAG CCC…

mutant ... CGT GGT GAG AGA GGA TTC CCT GGC TTG CCT GGC CCA TCG GG TGA GCC C…

exon number

(B) 1

(B) 2

normal ... ATC TGG TTT ... GGC TTC CAT TTC AGC TAT GGA GAT GAC...

exon number 5350 51 5249TT

mutant ... ATC TGT TCA GCT ATG GAG ATG ... AGA TGA...

normal ... CCC CTG CAG TAC ATG CGG GCC... ... .... CTG CTC ATC CAG

mutant ... CCC CTG deletion CTC ATC CAG GGC TCC...

c.4074+1G>T

(C) 1

(C) 2