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One decisive breakthrough as to this latter point was the finding that the key regulator of autophagy Beclin 1 harbours a BH3 domain [23] which binds to the BH1-BH2 dofanti-apoptoticpoptotic Bcl-2 [19] or Bcl-xL [24].
A second proband (II, Table 1) harbours a homozygous mutation in exon 2 of PDX1 (p.and2G; c.455C>G) and both unaffected parents are heterozygous.
The starting strain TMB3042 (Table 1) harbours genetic modifications previously reported to be favourable for pentose fermentation, such as overexpression of PPP [ 31] and XK [ 32] and deletion of GRE3, encoding an endogenous unspecific aldose reductase (AR) [ 33].
We wondered whether this was because Patient 1 harbours a mutation in the vWA domain, while the missense mutations in Patients 2 and 3 map to the Ig-like domain.
We hypothesise that this may be due to either the presence of upstream open reading frames in exons 5' to exon 1 (exon 1 harbours the preproghrelin start codon); expression of ghrelin locus derived transcripts lacking coding potential for ghrelin; or non-coding sense and/or antisense regulatory transcripts.
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