Figure 2 - uploaded by David Araujo-Vilar
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Splicing analysis and ampli fi cation of the BSCL2 c.985C>T and wild-type transcripts. (A) To con fi rm the hypothesis that the BSCL2 c.985C>T mutation results in a branch site (CCCCAG>CCCTAG) favouring splicing, the sequence of this gene in the region of the pathogenic mutation was analysed in silico with four splice site prediction programmes (*NNSPLICE 0.9, #Alternative Splice Site Predictor (ASSP), §NetGene2 v2.4 and † Human Splicing Finder v2.4.1). Human Splicing Finder v2.4.1, used to determine potential branch points, con fi rmed that the wild-type sequence (CCCCAG) has a consensus value of 86.03, whereas once mutated, the value of the branch point motif (CCCTAG) increases to 95.07. According to this computational tool, which is also able to establish potential splice sites, the mutated BSCL2 sequence analysed is predicted to have two splicing sites: a donor site at the beginning of intron 6 – 7 (CTGGGCTCAGgtgaggggcc) with a score of 96.91 † , and an acceptor site at the end of intron 7 – 8 (tcctccacagGTTAACATCC) with a score of 96.95 † . The same analysis was performed using NetGene2 v2.4§ and NNSPLICE 0.9*, which corroborate the presence of these splice sites: 0.96§* for the donor site and 0.96§ — 0.98* for the acceptor site. The ASSP tool was used to determine the constitutive or cryptic nature of the splice site: both donor and acceptor sites are constitutive, with high splice site scores of 14.346# and 13.11#, respectively. 20 (B) Results of the ampli fi cation of a 573 bp region of cDNA from lymphocytes, fi broblasts and preadipocytes from the index case and different control subjects. Only samples from the index case show the presence of a 431 base pair-long additional band (bands 2, 5 and 8). (C) Sequencing of the 431 base pair band showed complete skipping of exon 7.
Source publication
Background Seipin/BSCL2 mutations can cause type 2 congenital generalised lipodystrophy (BSCL) or dominant motor neurone diseases. Type 2 BSCL is frequently associated with some degree of intellectual impairment, but not to fatal neurodegeneration. In order to unveil the aetiology and pathogenetic mechanisms of a new neurodegenerative syndrome asso...
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