A case report of rare <i>ZC4H2</i>‐associated disorders associated with three large hernias

Nagara, Syunsuke; Fukaya, Satoko; Muramatsu, Yoshiyuki; Kaname, Tadashi; Tanaka, Taihei

doi:10.1111/ped.14211

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…Severe symptoms and even lethal phenotypes can manifest in both males and females, while mild or no symptoms are typically only observed in female patients. The various symptoms appear to correlate well with the different mutations in the ZC4H2 gene that have been reported [ 3 , 4 , 5 , 7 , 8 , 9 , 10 , 26 , 27 , 28 ].…”

Section: Discussionsupporting

confidence: 59%

Loss of Protein Function Causing Severe Phenotypes of Female-Restricted Wieacker Wolff Syndrome due to a Novel Nonsense Mutation in the ZC4H2 Gene

Sun

Cai

et al. 2022

Genes

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Pathogenic variants of zinc finger C4H2-type containing (ZC4H2) on the X chromosome cause a group of genetic diseases termed ZC4H2-associated rare disorders (ZARD), including Wieacker-Wolff Syndrome (WRWF) and Female-restricted Wieacker-Wolff Syndrome (WRWFFR). In the current study, a de novo c.352C>T (p.Gln118*) mutation in ZC4H2 (NM_018684.4) was identified in a female neonate born with severe arthrogryposis multiplex congenita (AMC) and Pierre-Robin sequence (cleft palate and micrognathia). Plasmids containing the wild-type (WT), mutant-type (MT) ZC4H2, or GFP report gene (N) were transfected in 293T cell lines, respectively. RT-qPCR and western blot analysis showed that ZC4H2 protein could not be detected in the 293T cells transfected with MT ZC4H2. The RNA seq results revealed that the expression profile of the MT group was similar to that of the N group but differed significantly from the WT group, indicating that the c.352C>T mutation resulted in the loss of function of ZC4H2. Differentially expressed genes (DEGs) enrichment analysis showed that c.352C>T mutation inhibited the expression levels of a series of genes involved in the oxidative phosphorylation pathway. Subsequently, expression levels of ZC4H2 were knocked down in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) by lentiviral-expressed small hairpin RNAs (shRNAs) against ZC4H2. The results also demonstrated that decreasing the expression of ZC4H2 significantly reduced the growth of NSCs by affecting the expression of genes related to the oxidative phosphorylation signaling pathway. Taken together, our results strongly suggest that ZC4H2 c.352C>T (p.Gln118*) mutation resulted in the loss of protein function and caused WRWFFR.

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Section: Discussionsupporting

confidence: 59%

Loss of Protein Function Causing Severe Phenotypes of Female-Restricted Wieacker Wolff Syndrome due to a Novel Nonsense Mutation in the ZC4H2 Gene

Sun

Cai

et al. 2022

Genes

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“…(b) In IFN-STAT1 signaling, K63-linked polyubiquitination of STAT1 at K110 by RNF220 promotes its interaction with JAK1 and its subsequent activation. RNF220 is also a target of STAT1 signaling (Guo et al, 2021) TA B L E 1 RNF220/ZC4H2 mutations or misregulation in human diseases Hirata et al, 2013;May et al, 2015;Nagara et al, 2020;Wang et al, 2020). AMCs are genetically heterogeneous and include various conditions affecting the formation or function of neuromuscular junctions (NMJs), skeletal muscles and bones, and the nervous system (Ma & Yu, 2017).…”

Section: Role S Of Rnf22 0 and Zc4h2 In Human Dis E A S E Smentioning

confidence: 99%

The many faces of the E3 ubiquitin ligase, RNF220, in neural development and beyond

Mao

2021

Dev Growth Differ

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Protein ubiquitination, an important posttranslational modification, is involved in almost all biological processes in eukaryotes (Zheng & Shabek, 2017). During embryonic development, protein ubiquitination plays a critical role in controlling signaling pathways that are essential for developmental patterning and determination of cell fate (Rape, 2017). Ubiquitination of target proteins is catalyzed by a three-step enzymatic cascade, including E1 ubiquitin-activating, E2 ubiquitin-conjugating, and E3 ubiquitin-ligating enzymes (Pickart, 2001). Ubiquitin has seven lysine (K) residues (K6, K11, K27, K29, K33, K48, and K63) that are involved in the formation polyubiquitin chains of different linkage types. Different linked polyubiquitin chains invoke various functional outcomes specific for each target protein. The most abundant polyubiquitin chains are K48-and K63linked chains, where the K48-linked chains function as a signal for

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A novel ZC4H2 variant in a female with severe respiratory complications

Wakabayashi

Mizukami

Terada

et al. 2022

Brain and Development

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A case report of rare ZC4H2‐associated disorders associated with three large hernias

Cited by 4 publications

References 5 publications

Loss of Protein Function Causing Severe Phenotypes of Female-Restricted Wieacker Wolff Syndrome due to a Novel Nonsense Mutation in the ZC4H2 Gene

Loss of Protein Function Causing Severe Phenotypes of Female-Restricted Wieacker Wolff Syndrome due to a Novel Nonsense Mutation in the ZC4H2 Gene

The many faces of the E3 ubiquitin ligase, RNF220, in neural development and beyond

A novel ZC4H2 variant in a female with severe respiratory complications

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