A Case of Mild Trichohepatoenteric Syndrome With New Variant Mutation in SKIV2L Gene: Case Report

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

Tomecki

Drążkowska

Kobyłecki

et al. 2023

WIREs RNA

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Trichohepatoenteric syndrome type 1: expanding the clinical spectrum of THES type 1 due to a homozygous variant in the SKIC3 gene

Alrammal,

Aljundi,

Abu Ghedda

et al. 2024

BMC Pediatr

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Trichohepatoenteric syndrome (THES), also known as phenotypic diarrhea or syndromic diarrhea, is a rare autosomal recessive genetic disorder caused by mutations in SKIC2 (THES-type 2) or SKIC3 (THES-type 1) and is characterized by early onset diarrhea, woolly brittle hair, facial dysmorphic features and liver disease. We report the case of a 24-month-old girl who presented with chronic diarrhea since the neonatal period along with intrauterine growth restriction (IUGR), developmental delay, dysmorphic features, congenital heart defects, liver disease, and recurrent infections. The diagnosis was made through whole-exome sequencing analysis, which detected a homozygous variant (c.4070del, p.Pro1357Leufs*10) in the SKIC3 gene. The patient required parenteral nutrition and was hospitalized for the first 10 months of life and then discharged on PN after showing improvement. She remained stable on PN after discharge despite a few admissions for central line infections. Recent follow-up at the age of 2 years revealed that she was stable on long-term parenteral nutrition and that she had advanced chronic liver disease.

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Trichohepatoenteric Syndrome: A Report of Two Children From Bahrain With a Novel Mutation and a Literature Review

Isa,

Matar,

Ali

et al. 2024

Cureus

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A Case of Mild Trichohepatoenteric Syndrome With New Variant Mutation in SKIV2L Gene: Case Report

Cited by 3 publications

References 13 publications

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

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

Trichohepatoenteric syndrome type 1: expanding the clinical spectrum of THES type 1 due to a homozygous variant in the SKIC3 gene

Trichohepatoenteric Syndrome: A Report of Two Children From Bahrain With a Novel Mutation and a Literature Review

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