NKAP is a ubiquitously expressed nucleoplasmic protein that is currently known as a transcriptional regulatory molecule via its interaction with HDAC3 and spliceosomal proteins. Here, we report a disorder of transcriptional regulation due to missense mutations in the X chromosome gene, NKAP. These mutations are clustered in the C-terminal region of NKAP where NKAP interacts with HDAC3 and post-catalytic spliceosomal complex proteins. Consistent with a role for the C-terminal region of NKAP in embryogenesis, nkap mutant zebrafish with a C-terminally truncated NKAP demonstrate severe developmental defects. The clinical features of affected individuals are highly conserved and include developmental delay, hypotonia, joint contractures, behavioral abnormalities, Marfanoid habitus, and scoliosis. In affected cases, transcriptome analysis revealed the presence of a unique transcriptome signature, which is characterized by the downregulation of long genes with higher exon numbers. These observations indicate the critical role of NKAP in transcriptional regulation and demonstrate that perturbations of the C-terminal region lead to developmental defects in both humans and zebrafish.

• MeSH
• dánio pruhované genetika   MeSH
• down regulace genetika   MeSH
• exony genetika   MeSH
• genetická transkripce genetika   MeSH
• geny vázané na chromozom X genetika   MeSH
• histondeacetylasy genetika   MeSH
• kognitivní dysfunkce genetika   MeSH
• lidé MeSH
• missense mutace genetika   MeSH
• regulace genové exprese genetika   MeSH
• represorové proteiny genetika   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH