Figure 7.

Suboptimal 5′ splice site of exon 3 underlies its alternative splicing and a predisposition to the NHD-associated mutation. Weak splicing signals are associated with alternative splicing. The 5′ splice site of TREM2 exon 3 is a weak splicing signal, which accounts for its alternative splicing. An NHD-associated GT-to-GC mutation (c.482 + 2 T > C) caused complete skipping of this exon. However, even in the presence of the GT-to-GC mutation, the GC-opt minigene showed nearly complete inclusion of exon 3, suggesting that the GT-to-GC mutation could have less deleterious effects if exon 3 had a stronger 5′ splice site.