Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion

Abstract

Roberts syndrome is an autosomal recessive disorder characterized by craniofacial anomalies, tetraphocomelia and loss of cohesion at heterochromatic regions of centromeres and the Y chromosome. We identified mutations in a new human gene, ESCO2, associated with Roberts syndrome in 15 kindreds. The ESCO2 protein product is a member of a conserved protein family that is required for the establishment of sister chromatid cohesion during S phase and has putative acetyltransferase activity.

Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes

“…Some of the more compelling clues include siblings that were diagnosed individually as RBS and SC (Romke et al 1987), the presence of chromosomal abnormalities in metaphase cells from both RBS and SC patients (Freeman et al 1974;Judge 1973;Tomkins et al 1979), and cell hybrid and chromosome transfer complementation studies indicating that they are caused by mutations in the same gene (McDaniel et al 2000;McDaniel et al 2005). Identification of Esco2/Efo2 mutations in both RBS and SC patients confirms their long-suspected relationship (Vega et al 2005;Schüle et al 2005). …”

“…Cornelia de Lange syndrome is caused by mutations in Nipped-B-Like (NIPBL), which encodes the human ortholog of Nipped-B and Scc2 Tonkin et al 2004), and in Smc1L1, which encodes the human Smc1 cohesin subunit (Musio et al 2006). The Roberts-SC phocomelia syndrome is caused by mutations in Esco2, one of the human orthologs of Ctf7/Eco1 (Vega et al 2005;Schüle et al 2005). Although the Cornelia de Lange and Roberts-SC phocomelia syndromes display similar developmental deficits, the molecular etiologies may differ significantly.…”

“…Roberts (OMIM #268300) and SC phocomelia (OMIM #269000) are genetically recessive syndromes caused by mutations in the Esco2/Efo2 homolog of Ctf7/Eco1 located at 8p21.1 (Vega et al 2005;Schüle et al 2005). RBS/SC and CdLS display similar characteristics, which include, but are not limited to, slow growth, mental retardation, and limb defects ( Table 2; Roberts 1919;Herrmann and Opitz 1977;Van den Berg and Francke 1993).…”

“…The Roberts syndrome gene was mapped using consanguineous families from Colombia, leading to the discovery of mutations in the Esco2/Efo2 gene (Vega et al 2005). Analysis of SC phocomelia families also uncovered novel Esco2 mutations (Schüle et al 2005).…”

Chromosome Dynamics during Mitosis

“…It has been proposed that the deacetylation reaction plays an important role in "recycling" used cohesin complexes for the next cell cycle. It is also important to note that deficiencies in this acetylation/deacetylation cycle of cohesin cause developmental diseases in humans, such as Roberts syndrome (Vega et al 2005) and Cornelia de Lange syndrome (Deardorff et al 2012).…”