UNC45A-related osteo-oto-hepato-enteric syndrome in a Chinese neonate

Kong, Ying; Ye, Chaoqun; Shi, Leyang; Dai, Qingmei; Wang, Ying; Hu, Jun; Wu, Xueyan; Shi, Mei-Yu; Hu, Xiaofeng; Huang, Huizhi

doi:10.1016/j.ejmg.2022.104693

Cited by 2 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several genetic variants of UNC-45A have been linked to rare genetic disorders such as the osteo-oto-hepato-enteric syndrome, the Aagenaes Syndrome, and the congenital diarrheal disorder [ 133 , 134 , 135 , 136 , 137 ] ( Table 3 ). The disease-causing mutations are located in different regions of the UNC-45A gene, ranging from the 5′ untranslated region to the C-terminal UCS domain [ 133 , 134 , 135 , 136 , 137 ]. Many of these mutations decrease the protein level of UNC-45A in patients’ cells, indicating that the loss of UNC-45A expression and function is a causal driver of these diseases [ 133 , 136 , 137 ].…”

Section: Unc-45amentioning

confidence: 99%

“…Osteo-oto-hepatic-enteric syndrome Diarrhea, cholestasis, and impaired hearing [133][134][135] UNC-45A mutants decreasing its expression Aagenaes syndrome Cholestasis and lymphedema [136] UNC-45A mutants decreasing its expression Congenital diarrhea disorder Diarrhea, duodenal villous atrophy, erosion of apical microvilli [137] Chemically induced UNC-45A mutation Zebrafish Apical vacuolar inclusions, microvilli shortening [137] UNC-45 mutants decreasing its expression Drosophila Increased intestinal permeability [138] CRISPR/Cas9-mediated knockout of UNC-45A…”

Section: Unc-45a Mutants Decreasing Its Expressionmentioning

confidence: 99%

“…Increased barrier permeability, AJ and TJ disassembly, disorganization of the perijunctional actomyosin belt [138] Several genetic variants of UNC-45A have been linked to rare genetic disorders such as the osteo-oto-hepato-enteric syndrome, the Aagenaes Syndrome, and the congenital diarrheal disorder [133][134][135][136][137] (Table 3). The disease-causing mutations are located in different regions of the UNC-45A gene, ranging from the 5 ′ untranslated region to the C-terminal UCS domain [133][134][135][136][137]. Many of these mutations decrease the protein level of UNC-45A in patients' cells, indicating that the loss of UNC-45A expression and function is a causal driver of these diseases [133,136,137].…”

Section: Sk-co15 and Ht-29 Human Colonic Epithelial Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Lechuga,

Marino-Melendez,

Naydenov

et al. 2024

Cells

View full text Add to dashboard Cite

The integrity and permeability of epithelial and endothelial barriers depend on the formation of tight junctions, adherens junctions, and a junction-associated cytoskeleton. The establishment of this junction–cytoskeletal module relies on the correct folding and oligomerization of its protein components. Molecular chaperones are known regulators of protein folding and complex formation in different cellular compartments. Mammalian cells possess an elaborate chaperone network consisting of several hundred chaperones and co-chaperones. Only a small part of this network has been linked, however, to the regulation of intercellular adhesions, and the systematic analysis of chaperone functions at epithelial and endothelial barriers is lacking. This review describes the functions and mechanisms of the chaperone-assisted regulation of intercellular junctions. The major focus of this review is on heat shock protein chaperones, their co-chaperones, and chaperonins since these molecules are the focus of the majority of the articles published on the chaperone-mediated control of tissue barriers. This review discusses the roles of chaperones in the regulation of the steady-state integrity of epithelial and vascular barriers as well as the disruption of these barriers by pathogenic factors and extracellular stressors. Since cytoskeletal coupling is essential for junctional integrity and remodeling, chaperone-assisted assembly of the actomyosin cytoskeleton is also discussed.

show abstract

Section: Unc-45amentioning

confidence: 99%

Section: Unc-45a Mutants Decreasing Its Expressionmentioning

confidence: 99%

Section: Sk-co15 and Ht-29 Human Colonic Epithelial Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Lechuga,

Marino-Melendez,

Naydenov

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

Intracellular Trafficking Defects in Congenital Intestinal and Hepatic Diseases

Szabó,

Pollio,

Vogel

2024

Traffic

View full text Add to dashboard Cite

Enterocytes and liver cells fulfill important metabolic and barrier functions and are responsible for crucial vectorial secretive and absorptive processes. To date, genetic diseases affecting metabolic enzymes or transmembrane transporters in the intestine and the liver are better comprehended than mutations affecting intracellular trafficking. In this review, we explore the emerging knowledge on intracellular trafficking defects and their clinical manifestations in both the intestine and the liver. We provide a detailed overview including more investigated diseases such as the canonical, variant and associated forms of microvillus inclusion disease, as well as recently described pathologies, highlighting the complexity and disease relevance of several trafficking pathways. We give examples of how intracellular trafficking hubs, such as the apical recycling endosome system, the trans‐Golgi network, lysosomes, or the Golgi‐to‐endoplasmic reticulum transport are involved in the pathomechanism and lead to disease. Ultimately, understanding these processes could spark novel therapeutic approaches, which would greatly improve the quality of life of the affected patients.

show abstract

UNC45A-related osteo-oto-hepato-enteric syndrome in a Chinese neonate

Cited by 2 publications

References 25 publications

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Intracellular Trafficking Defects in Congenital Intestinal and Hepatic Diseases

Contact Info

Product

Resources

About