Intronic mutations in 18 TSC NMI subjects.

<p>The locations of 18 splice site mutations identified are shown relative to the canonical consensus sequences present at the 3’ exon region, the branch site, and the 5’ exon region.</p

Mutations identified in the TSC NMI subjects.

<p>Column 1 is subject number. f means that this was a familial case of TSC. All others had no family history of TSC.</p><p>Column 3, letters next to splice site variants</p><p>^A variants affecting canonical splice sites</p><p>^B reported as affecting splicing and / or being pathogenic</p><p>^C aberrant TSC2 transcripts shown in this study</p><p>^D high molecular weight product by RT-PCR of RNA, or allelic distortion of exonic SNPs by RT-PCR analysis</p><p>^E intronic variants not seen previously, that were de novo (n = 1) or segregated with TSC (n = 2), without other confirmatory evidence of effect on splicing.</p><p>^{^}In P14 and P43 mutations were detected in skin lesions but not in blood or saliva samples (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005637#pgen.1005637.s005" target="_blank">S2 Table</a>).</p><p>^# Identified by MLPA.</p><p>Column 7 gives the age of the subject at the time of collection of clinical data.</p><p>Columns 9–12 indicate the presence or absence of involvement of Skin (S), Brain (B), Heart (H), Kidneys (K), Lungs (L). A blank entry in these columns means no involvement of the respective organ; a number entry indicates the number of major TSC manifestations present in the subject for that organ.</p><p>Mutations identified in the TSC NMI subjects.</p

Correlation between clinical features and mutation status in 53 NMI subjects.

<p>(A) The proportion of subjects with 2, 3, or 4 organs affected; with heterozygous or mosaic mutations, or persistent NMI status. P = 0.003. (B) The number of major symptoms seen for each subject sorted according to mutation status. Note that differing levels of mosaicism have different symbols according to allele frequency (AF). (C) Age at the time of clinical evaluation, sorted according to mutation status. Het, heterozygous; Mos, mosaic. P values determined by chi square test (A) and Mann-Whitney unpaired test (B and C). Results with p < 0.05 are considered statistically significant.</p

Pie charts displaying the mutation types and frequencies in 53 TSC NMI subjects.

<p>(A) Proportion of subjects with mutations identified vs. remaining as persistent NMI. (B) Proportion of mutations in <i>TSC1</i> vs. <i>TSC2</i>. (C) Proportion of heterozygous vs. mosaic mutations. (D) Different types of identified mutations.</p