Hyper IgM in tricho-hepato-enteric syndrome due to TTC37 mutation

Kristal, Eyal; Nahum, Amit; Ling, Galina; Broides, Arnon; Shubinsky, George; Eskin‐Schwartz, Marina; Hadar, Noam; Progador, Omri; Birk, Ohad S.

doi:10.1007/s12026-022-09305-9

Cited by 3 publications

(3 citation statements)

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“…example, hypogammaglobulinemia in IgG; monoclonal hyper IgA; T and NK cell lymphopenia; hyper IgM; reduced number of memory B cells and low counts of switched memory B lymphocytes; impaired IFN-γ production by T and NK cells, associated with a reduced degranulation of NK cells, which indicates problem with their activation following, for example, pharmacological stimulation; defects in antibody production after vaccination-decreased or absent response; increased vulnerability to frequent opportunistic viral and bacterial infections; Chong et al, 2015;Fabre et al, 2011Fabre et al, , 2012Fabre et al, , 2013Kinnear et al, 2017;Kristal et al, 2022;Vely et al, 2018). The next two symptoms are frequent and include: (6) skin abnormalities (xerosis; rubbery skin; lentigines; café-au-lait spots-sometimes hyperpigmentation is limited to specific body parts, such as pelvic girdle and lower limb in a cohort of patients from Saudi Arabia; one extreme case of pyoderma gangrenosum-like skin lesions was also described; Chong et al, 2015;Fabre et al, 2012Fabre et al, , 2013Karaca Edeer et al, 2019;Monies et al, 2015); and (7) liver disease (mildly elevated liver enzymes, hepatic hemangiomas, siderosis, fibrosis, cirrhosis; Fabre et al, 2012Fabre et al, , 2013.…”

Section: Thes Symptoms and Disease Managementmentioning

confidence: 99%

“…Three of them are present in the vast majority of cases: (1) intractable chronic diarrhea, usually with early onset, leading to malabsorption and failure to thrive; (2) facial dysmorphism (coarse features, hypertelorism, broad flat nasal bridge, prominent forehead and cheeks, low‐set ears, large mouth); and (3) hair abnormalities (fragile/brittle, sparse, coarse, woolly, patchy, uncombable, easily removable, and poorly pigmented hair with trichorrhexis nodosa ) (Fabre et al, 2011, 2012, 2013, 2014). Another two symptoms are very frequent: (4) intrauterine growth restriction (IUGR); and (5) immunodeficiency (reflected by, for example, hypogammaglobulinemia in IgG; monoclonal hyper IgA; T and NK cell lymphopenia; hyper IgM; reduced number of memory B cells and low counts of switched memory B lymphocytes; impaired IFN‐γ production by T and NK cells, associated with a reduced degranulation of NK cells, which indicates problem with their activation following, for example, pharmacological stimulation; defects in antibody production after vaccination—decreased or absent response; increased vulnerability to frequent opportunistic viral and bacterial infections; Chong et al, 2015; Fabre et al, 2011, 2012, 2013, 2014; Kinnear et al, 2017; Kristal et al, 2022; Vely et al, 2018). The next two symptoms are frequent and include: (6) skin abnormalities (xerosis; rubbery skin; lentigines; café‐au‐lait spots—sometimes hyperpigmentation is limited to specific body parts, such as pelvic girdle and lower limb in a cohort of patients from Saudi Arabia; one extreme case of pyoderma gangrenosum ‐like skin lesions was also described; Chong et al, 2015; Fabre et al, 2012, 2013, 2014; Karaca Edeer et al, 2019; Monies et al, 2015); and (7) liver disease (mildly elevated liver enzymes, hepatic hemangiomas, siderosis, fibrosis, cirrhosis; Fabre et al, 2012, 2013, 2014).…”

Section: Trichohepatoenteric Syndrome (Thes)—a Major Clinical Manifes...mentioning

confidence: 99%

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SKI complex: A multifaceted cytoplasmic RNA exosome cofactor in mRNA metabolism with links to disease, developmental processes, and antiviral responses

et al. 2023

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RNA stability and quality control are integral parts of gene expression regulation. A key factor shaping eukaryotic transcriptomes, mainly via 3′–5′ exoribonucleolytic trimming or degradation of diverse transcripts in nuclear and cytoplasmic compartments, is the RNA exosome. Precise exosome targeting to various RNA molecules requires strict collaboration with specialized auxiliary factors, which facilitate interactions with its substrates. The predominant class of cytoplasmic RNA targeted by the exosome are protein‐coding transcripts, which are carefully scrutinized for errors during translation. Normal, functional mRNAs are turned over following protein synthesis by the exosome or by Xrn1 5′–3′‐exonuclease, acting in concert with Dcp1/2 decapping complex. In turn, aberrant transcripts are eliminated by dedicated surveillance pathways, triggered whenever ribosome translocation is impaired. Cytoplasmic 3′–5′ mRNA decay and surveillance are dependent on the tight cooperation between the exosome and its evolutionary conserved co‐factor—the SKI (superkiller) complex (SKIc). Here, we summarize recent findings from structural, biochemical, and functional studies of SKIc roles in controlling cytoplasmic RNA metabolism, including links to various cellular processes. Mechanism of SKIc action is illuminated by presentation of its spatial structure and details of its interactions with exosome and ribosome. Furthermore, contribution of SKIc and exosome to various mRNA decay pathways, usually converging on recycling of ribosomal subunits, is delineated. A crucial physiological role of SKIc is emphasized by describing association between its dysfunction and devastating human disease—a trichohepatoenteric syndrome (THES). Eventually, we discuss SKIc functions in the regulation of antiviral defense systems, cell signaling and developmental transitions, emerging from interdisciplinary investigations.This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes

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Section: Thes Symptoms and Disease Managementmentioning

confidence: 99%

Section: Trichohepatoenteric Syndrome (Thes)—a Major Clinical Manifes...mentioning

confidence: 99%

SKI complex: A multifaceted cytoplasmic RNA exosome cofactor in mRNA metabolism with links to disease, developmental processes, and antiviral responses

et al. 2023

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“…Affected infants generally require parenteral nutrition, but there have been reports of enteral autonomy acquired with age (Hartley et al 2010 ). THES is also associated with an immune dysregulation phenotype which has been compared to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-disease, and Hyper IgM syndrome (Baxter et al 2022 ; Kristal et al 2022 ).…”

Section: Epithelial Structure Trafficking and Polaritymentioning

confidence: 99%

The genetics of monogenic intestinal epithelial disorders

2022

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Monogenic intestinal epithelial disorders, also known as congenital diarrheas and enteropathies (CoDEs), are a group of rare diseases that result from mutations in genes that primarily affect intestinal epithelial cell function. Patients with CoDE disorders generally present with infantile-onset diarrhea and poor growth, and often require intensive fluid and nutritional management. CoDE disorders can be classified into several categories that relate to broad areas of epithelial function, structure, and development. The advent of accessible and low-cost genetic sequencing has accelerated discovery in the field with over 45 different genes now associated with CoDE disorders. Despite this increasing knowledge in the causal genetics of disease, the underlying cellular pathophysiology remains incompletely understood for many disorders. Consequently, clinical management options for CoDE disorders are currently limited and there is an urgent need for new and disorder-specific therapies. In this review, we provide a general overview of CoDE disorders, including a historical perspective of the field and relationship to other monogenic disorders of the intestine. We describe the genetics, clinical presentation, and known pathophysiology for specific disorders. Lastly, we describe the major challenges relating to CoDE disorders, briefly outline key areas that need further study, and provide a perspective on the future genetic and therapeutic landscape.

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