A Review of campomelic dysplasia syndrome

This chapter further discusses bone dysplasias and includes discussion on campomelic dysplasia, cousin dysplasia, spondylo-megaepiphyseal-metaphyseal dysplasia, cleidocranial dysplasia, Yunis-Varon syndrome, CDAGS, nail-patella syndrome, ischio-pubic-patellar dysplasia, ischiospinal dysostosis, and cerebro-costo-mandibular syndrome. Each discussion includes major radiographic features, major clinical findings, genetics, major differential diagnoses, and a bibliography.

Download Full-text

The SOXE transcription factors—SOX8, SOX9 and SOX10—share a bi-partite transactivation mechanism

Nucleic Acids Research ◽

10.1093/nar/gkz523 ◽

2019 ◽

Vol 47 (13) ◽

pp. 6917-6931 ◽

Cited By ~ 7

Author(s):

Abdul Haseeb ◽

Véronique Lefebvre

Keyword(s):

Transcription Factors ◽

Cell Fate ◽

Binding Pocket ◽

Molecular Networks ◽

Transactivation Domain ◽

Campomelic Dysplasia ◽

Incomplete Knowledge ◽

Evolutionarily Conserved ◽

Sox Proteins ◽

Disease Understanding

Abstract SOX8, SOX9 and SOX10 compose the SOXE transcription factor group. They govern cell fate and differentiation in many lineages, and mutations impairing their activity cause severe diseases, including campomelic dysplasia (SOX9), sex determination disorders (SOX8 and SOX9) and Waardenburg-Shah syndrome (SOX10). However, incomplete knowledge of their modes of action limits disease understanding. We here uncover that the proteins share a bipartite transactivation mechanism, whereby a transactivation domain in the middle of the proteins (TAM) synergizes with a C-terminal one (TAC). TAM comprises amphipathic α-helices predicted to form a protein-binding pocket and overlapping with minimal transactivation motifs (9-aa-TAD) described in many transcription factors. One 9-aa-TAD sequence includes an evolutionarily conserved and functionally required EΦ[D/E]QYΦ motif. SOXF proteins (SOX7, SOX17 and SOX18) contain an identical motif, suggesting evolution from a common ancestor already harboring this motif, whereas TAC and other transactivating SOX proteins feature only remotely related motifs. Missense variants in this SOXE/SOXF-specific motif are rare in control individuals, but have been detected in cancers, supporting its importance in development and physiology. By deepening understanding of mechanisms underlying the central transactivation function of SOXE proteins, these findings should help further decipher molecular networks essential for development and health and dysregulated in diseases.

Download Full-text