Vega, H. et al. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion. Nature Genet. 37, 468-470
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.
Full-textDOI: · Available from: Ethylin Wang Jabs, Sep 28, 2015
- SourceAvailable from: Najim Ameziane
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- "(/BRCA2) p.Ala938Profs*21 p.Lys3326* EUFA178-L M FANCB a Deletion promoter exon 1 –  No protein EUFA1386-L M FANCB a c.829dup –  p.Cys277Leufs*31 EUFA158-L F FANCC c.67del (also known as 322delG) c.67del (also known as 322delG)  p.Asp23Ilefs*23 p.Asp23Ilefs*23 EUFA1289-L M FANCD2 c.206-2A > T c.1414- 71 1545 + 256del459  p.Ala69Aspfs*7 p.Glu472 Lys515del EUFA816-L M FANCI c.3853C > T c.3350-88A > G  p.Arg1285* p.Glu1117fs EUFA868-L F FANCL c.837-15 837-9delins177 c.837-15 837-9delins177  p.? p.? EUFA867-L F FANCM c.2171C > A c.4222 + 1978 4300del  p.Ser724* p.? FANCA c.2557C > T c.709 + 5G > A  p.Arg853* p.? HSC62 M FANCD1 c.8488-1G > A c.8488-1G > A  (/BRCA2) p.Trp2830 Lys2833del p.Trp2830 Lys2833del EUFA208-L F FANCD1 c.7878G > C c.756 757del Current study (/BRCA2) p.Trp2626Cys p.Asp252Glufs*2 EUFA423-L F FANCD1 c.7463 7464insAT c.9672dup  (/BRCA2) p.Asp2489* p.Tyr3225Ilefs*30 EUFA579-L F FANCD1 c.7007G > A 5609 5610delinsAG  (/BRCA2) p.? p.Phe1870* EUFA932-L M FANCD1 c.2957dup c.7684T > C Current study (/BRCA2) p.Asn986Lysfs*2 p.Phe2562Leu EUFA943-L M FANCD1 c.480 489del c.480 489del Current study (/BRCA2) p.Gly162Phefs*7 p.Gly162Phefs*7 EUFA1389-L F FANCD1 c.1597del Deletion exon 15–16 Current study (BRCA2) p.Thr533Leufs*25 p.? EUFA696-L F FANCJ c.2392C > T c.2492 + 2dup  (/BRIP1) p.Arg798* p.? EUFA1341-L F FANCN c.1653T > A Deletion exon 1–10  (/PALB2) p.Tyr551* p.? EUFA1354-L M FANCP c.286del c.286del  (/SLX4) p.Thr96Leufs*30 p.Thr96Leufs*30 FA104 F FANCQ c.1484 1488del c.2065C > A  (/XPF) p.Thr495Asnfs*6 p.Arg689Ser VU1177-L F ESCO2 c.1111dup c.1111dup  p.Thr371Asnfs*32 p.Thr371Asnfs*32 VU1199-L M ESCO2 c.879 880del c.879 880del  p.Arg293Serfs*7 p.Arg293Serfs*7 VU1202-L M DDX11 c.2689 2691del c.2271 + 2T > C  p. Lys897del p.? CdLS11165 M NIPBL b c.3813 3815del –  p.Lys1271del CdLS11167 F NIPBL b c.3940dup –  p.Thr1314Asnfs*9 EUFA1341F SV40 F FANCN c.1653T > A Deletion exon 1–10  (/PALB2) p.Tyr551* p.? VU1199F SV40 M ESCO2 c.879 880del c.879 880del  p.Arg293Serfs*7 p.Arg293Serfs*7 VU-SCC-1131 F FANCC c.67del (also known as 322delG) c.67del (also known as 322delG)  p.Asp23Ilefs*23 p.Asp23Ilefs*23 VU-SCC-1365 M FANCA c.3788-3790del c.3788-3790del  p. Phe1263del p.Phe1263del VU-SCC-1604 F FANCL c.483 487del c.906C > G Current study p.Glu161Aspfs*31 p.Ile302Met a X-linked inheritance. b Autosomal dominant "
ABSTRACT: The encouraging response rates of BRCA1- and BRCA2-mutated cancers toward PARP inhibitors make it worthwhile to identify other potential determinants of PARP inhibitor responsiveness. Since the Fanconi anemia (FA) pathway coordinates several DNA repair pathways, including homologous recombination in which BRCA1 and BRCA2 play important roles, we investigated whether this pathway harbors other predictors of PARP inhibitor sensitivity. Lymphoblastoid cell lines derived from individuals with FA or clinically related syndromes, such as Warsaw breakage syndrome, were tested for PARP inhibitor sensitivity. Remarkably, we found a strong variability in PARP inhibitor sensitivity among different FANCD1/BRCA2-deficient lymphoblasts, suggesting that PARP inhibitor response depends on the type of FANCD1/BRCA2 mutation. We identified the DNA helicases FANCM and DDX11 as determinants of PARP inhibitor response. These results may extend the utility of PARP inhibition as effective anticancer treatment. Copyright © 2014 Elsevier B.V. All rights reserved.DNA Repair 12/2014; 26. DOI:10.1016/j.dnarep.2014.12.003 · 3.11 Impact Factor
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- "In addition to Aurora kinases, several members of the HAT family are also significantly upregulated in arthritic mice and patients with RA, with the gene encoding Esco2 showing the strongest increase in expression. Esco2 is thought to be required for the establishment of sister chromatid cohesion and it also couples cohesion and DNA replication to ensure that only sister chromatids are paired together [23,24]. Because Esco2 belongs to the HAT family of epigenetic modifiers, it is reasonable to assume that it acts as a selective activator of certain target genes. "
ABSTRACT: An increasing number of studies show that besides the inherited genetic architecture (that is, genomic DNA), various environmental factors significantly contribute to the etiology of rheumatoid arthritis. Epigenetic factors react to external stimuli and form bridges between the environment and the genetic information-harboring DNA. Epigenetic mechanisms are implicated in the final interpretation of the encoded genetic information by regulating gene expression, and alterations in their profile influence the activity of the immune system. Overall, epigenetic mechanisms further increase the well-known complexity of rheumatoid arthritis by providing additional subtle contributions to rheumatoid arthritis susceptibility. Although there are controversies regarding the involvement of epigenetic and genetic factors in rheumatoid arthritis etiology, it is becoming obvious that the two systems (genetic and epigenetic) interact with each other and are ultimately responsible for rheumatoid arthritis development. Here, epigenetic factors and mechanisms involved in rheumatoid arthritis are reviewed and new, potential therapeutic targets are discussed.BMC Medicine 02/2014; 12(1):35. DOI:10.1186/1741-7015-12-35 · 7.25 Impact Factor
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- "Roberts syndrome (RBS, MIM 268300) is characterized by pre-and post-natal growth retardation, bilateral symmetric limb reduction, and craniofacial abnormalities including hypertelorism, cleft lip and palate, and hypoplastic nasal alae . RBS is inherited in an autosomal recessive manner and is caused by mutations in the ESCO2 gene , which have been recently shown to influence production of rRNA . ESCO2, Establishment of Cohesion 1 Homolog 2 (Eco1 in yeast), is an acetyl transferase important in assembly of Cohesin. "
ABSTRACT: The skeleton affords a framework and structural support for vertebrates, while also facilitating movement, protecting vital organs, and providing a reservoir of minerals and cells for immune system and vascular homeostasis. The mechanical and biological functions of the skeleton are inextricably linked to the size and shape of individual bones, the diversity of which is dependent in part upon differential growth and proliferation. Perturbation of bone development, growth and proliferation, can result in congenital skeletal anomalies, which affect approximately 1 in 3000 live births . Ribosome biogenesis is integral to all cell growth and proliferation through its roles in translating mRNAs and building proteins. Disruption of any steps in the process of ribosome biogenesis can lead to congenital disorders termed ribosomopathies. In this review, we discuss the role of ribosome biogenesis in skeletal development and in the pathogenesis of congenital skeletal anomalies. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.Biochimica et Biophysica Acta 11/2013; 1842(6). DOI:10.1016/j.bbadis.2013.11.010 · 4.66 Impact Factor