Syndromic (phenotypic) diarrhoea of infancy/tricho-hepato-enteric syndrome

Fabre, Alexandre; Breton, A; Coste, Marie-Edith; Colomb, V.; Dubern, B.; Lachaux, Alain; Lemale, Julie; Mancini, Julien; Marinier, Evelyne; Martinez-Vinson, Christine; Peretti, Noël; Perry, Ariane; Roquelaure, Bertrand; Venaille, Aude; Sarles, J.; Goulet, Olivier; Badens, Catherine

doi:10.1136/archdischild-2013-304016

Cited by 51 publications

(72 citation statements)

References 19 publications

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“…Moreover, it often remains unclear if weaned patients have a good nutritional status or if some level of parenteral nutrition may still be useful. It has already been noted that SD/THE patients are of small stature despite adequate nutrition (11,35) and that in two patients growth hormone administration failed to improve growth (35).…”

Section: Discussionmentioning

confidence: 97%

“…Except for some cases (19,24), it is not clear whether the absence of parenteral nutrition was due to non-availability or for some other reason. With parenteral nutrition, weaning can be achieved in nearly 50% of the patients as already reported in the literature (35). One of the limits with this approach is that it can also reflect different practices in different countries.…”

Section: Discussionmentioning

confidence: 99%

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Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Fabre

Bourgeois

Coste

et al. 2017

IRDR

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Fabre

Bourgeois

Coste

et al. 2017

IRDR

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“…The mortality is high with one third of the children deceased before 10 years. About half of the children can be weaned off parenteral nutrition and nearly all have a small size below the 3 rd percentile (8). The phenotypes resulting from an alteration of either SKIV2L or TTC37 cannot be differentiated, suggesting that it is the absence of the SKI complex which is responsible for the disease.…”

Section: Discussionmentioning

confidence: 99%

Human Mendelian diseases related to abnormalities of the RNA exosome or its cofactors

Fabre

Badens

2014

IRDR

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“…Mutations in SKI complex genes have been linked to tricho-hepato-enteric (THE) syndrome, which causes intestinal failure (Hartley et al 2010;Fabre et al 2012Fabre et al , 2013. In addition, mutations in the DIS3 catalytic subunit gene have been implicated in multiple myeloma (Chapman et al 2011;Tomecki et al 2013;Robinson et al 2015).…”

mentioning

confidence: 99%

Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast

et al. 2017

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Pontocerebellar hypoplasia type 1b (PCH1b) is an autosomal recessive disorder that causes cerebellar hypoplasia and spinal motor neuron degeneration, leading to mortality in early childhood. PCH1b is caused by mutations in the RNA exosome subunit gene, EXOSC3. The RNA exosome is an evolutionarily conserved complex, consisting of nine different core subunits, and one or two 39-59 exoribonuclease subunits, that mediates several RNA degradation and processing steps. The goal of this study is to assess the functional consequences of the amino acid substitutions that have been identified in EXOSC3 in PCH1b patients. To analyze these EXOSC3 substitutions, we generated the corresponding amino acid substitutions in the Saccharomyces cerevisiae ortholog of EXOSC3, Rrp40. We find that the rrp40 variants corresponding to EXOSC3-G31A and -D132A do not affect yeast function when expressed as the sole copy of the essential Rrp40 protein. In contrast, the rrp40-W195R variant, corresponding to EXOSC3-W238R in PCH1b patients, impacts cell growth and RNA exosome function when expressed as the sole copy of Rrp40. The rrp40-W195R protein is unstable, and does not associate efficiently with the RNA exosome in cells that also express wild-type Rrp40. Consistent with these findings in yeast, the levels of mouse EXOSC3 variants are reduced compared to wild-type EXOSC3 in a neuronal cell line. These data suggest that cells possess a mechanism for optimal assembly of functional RNA exosome complex that can discriminate between wildtype and variant exosome subunits. Budding yeast can therefore serve as a useful tool to understand the molecular defects in the RNA exosome caused by PCH1b-associated amino acid substitutions in EXOSC3, and potentially extending to disease-associated substitutions in other exosome subunits.KEYWORDS pontocerebellar hypoplasia type 1b; RNA exosome; EXOSC3; Rrp40; EXOSC2; RNA processing/degradation T HE RNA exosome is an evolutionarily conserved ribonuclease complex that is responsible for several essential RNA processing and degradation steps (Mitchell et al. 1997;Allmang et al. 1999;Schneider and Tollervey 2013). Major exosome substrates include mRNA, rRNA, and small RNAs. In addition to degrading aberrant and unneeded transcripts, the RNA exosome also trims precursor RNAs, including 5.8S rRNA (Mitchell et al. 1996). The RNA exosome thus plays critical roles in both RNA degradation and maturation.The subunits of the RNA exosome complex are evolutionarily conserved and many were first identified in Saccharomyces cerevisiae in a screen for ribosomal RNA processing (rrp) mutants (Mitchell et al. 1996(Mitchell et al. , 1997Allmang et al. 1999). S. cerevisiae Rrp subunits correspond to human EXOSC subunits. The functions of the RNA exosome have been extensively characterized in budding yeast (Sloan et al. 2012), and many are conserved in humans (Schilders et al. 2005;Staals et al. 2010;Lubas et al. 2011Lubas et al. , 2015 the RNA exosome, six subunits comprise a core ring, and three putative RNA-binding sub...

show abstract

Syndromic (phenotypic) diarrhoea of infancy/tricho-hepato-enteric syndrome

Abstract: SD/THE is a rare disease with high morbidity and mortality. Management should be focused on nutrition and immunological defects.

Cited by 51 publications

References 19 publications

Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Human Mendelian diseases related to abnormalities of the RNA exosome or its cofactors

Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast

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