PMC:3654953 / 19259-20452 JSONTXT

{"project":"2_test","denotations":[{"id":"23634874-16680138-81641088","span":{"begin":146,"end":148},"obj":"16680138"},{"id":"23634874-12024216-81641089","span":{"begin":934,"end":936},"obj":"12024216"},{"id":"T38509","span":{"begin":146,"end":148},"obj":"16680138"},{"id":"T78028","span":{"begin":934,"end":936},"obj":"12024216"}],"text":"To test whether additional genes could influence phenotype expression, 18 genes with variants in Pt2 were prioritized by the Endeavour software, [21] using “training genes” associated with MND (Additional file 6). The highest score was achieved by HDAC6, on chromosome Xp11.23, encoding a member of the histone deacetylase family (NP_006035.2); Pt2 was hemizygous for a c. 2566C\u003eT/p.P856S, variant, whereas Pt1, II-6 and II-7 were wt, and the mother, I-2, was heterozygous (Figure 3A). Whilst the variants in the other genes were all relatively frequent SNPs and/or present also in Pt1 (Additional file 6), the P856S change was absent in all available databases, including EVS. The amount of HDAC6 transcripts was similar in fibroblasts from Pt2 vs. Pt1 or control subjects, indicating that neither HDAC6 expression nor stability is severly affected by the mutation (Figure 3B). However, acetylated alpha-tubulin, a HDAC6 substrate, [22] was consistently increased (Figure 3C); treatment of fibroblasts with tubacin, a selective HDAC6 inhibitor, clearly increased the acetylation of alpha-tubulin, confirming the specificity of this assay to detect impaired HDAC6 activity (Additional file 7)."}