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.

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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. exon 6 exon 8 exon 5 intron 5 intron 5 exon 6 (A) 1 & 2 normal ...CAG insertion GGA GGT ... GGA AAC TTT GCT ... mutant ...CAG gta...taa... cag GGA deletion AAC TTT GCT ... c.430-1G>C exon number 4 5 6 7 8 AC normal ... GGT GAA AAA GGT ... GGA AAC TTT GCT ... mutant ... GGT GAA AAA GTG ...TGG A AC TTT GCT ... GTA ATG exon 6 exon 7 (A) 3

41 42 43 44 (B) 1 c.3003+5G>A GTGAA (B) 2 exon 42 exon 43 exon 44 normal ... GGT CCC TCT GGT GCC GAA ... GGT GAG CCC... mutant ... GGT CCC TCT deletion GGT GAG CCC ... c.3003+5G>A 41 42 43 44 exon number GTGAA 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… (B) 2

(C) 1 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 exon number 49 50 51 52 53 TT normal ... ATC TGG TTT ... GGC TTC CAT TTC AGC TAT GGA GAT GAC... mutant ... ATC TGT TCA GCT ATG GAG ATG ... AGA TGA... (C) 2