ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/043/SRR20187043/SRR20187043_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/046/SRR20187046/SRR20187046_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/045/SRR20187045/SRR20187045_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/048/SRR20187048/SRR20187048_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/043/SRR20187043/SRR20187043_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/044/SRR20187044/SRR20187044_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/047/SRR20187047/SRR20187047_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/046/SRR20187046/SRR20187046_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/048/SRR20187048/SRR20187048_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/047/SRR20187047/SRR20187047_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/045/SRR20187045/SRR20187045_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR201/044/SRR20187044/SRR20187044_1.fastq.gzprimary200OKGenomicsShanghai Children’s Hospital, Shanghai Institute of Medical Genetics, Shanghai Jiao Tong University School of Medicinehttps://www.ebi.ac.uk/ena/browser/view/PRJNA858652Homo sapiensBackground: Pathogenic variants of zinc finger C4H2-type containing (ZC4H2) on the X chromosome caused a group of genetic diseases called ZC4H2-associated rare disorders (ZARD), including Wieacker-Wolff Syndrome (WRWF) and Female-restricted Wieacker-Wolff Syndrome (WRWFFR). Patients displayed arthrogryposis multiplex congenita (AMC), central and peripheral nervous system involvement, as well as multiple dysmorphic features. The underlying mechanisms of the complex syndrome remain to be elucidated. Methods: Expression levels of ZC4H2 were knockdown in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) by lentiviral-expressed shRNAs against ZC4H2. RNA sequencing (RNA seq) was subsequently applied to study the effects on gene expression profiles. The expression levels of differentially expressed genes were then verified by PCR array and RT-qPCR. Results: neural stem cell-like cells were induced from human induced pluripotent stem cells (hiPSCs), which were confirmed to express biomarkers of Neural stem cells (NSCs) by immunofluorescence. The viability of NSCs were affected through inhibition of ZC4H2 expression after they were infected with lentivirus containing siRNA targeting to ZC4H2 gene. The RNA-seq results showed that the gene expression pattern in NSCs was changed after inhibition of ZC4H2. DEGs were significantly enriched in oxidative phosphorylation and neurodegenerative diseases signaling pathways. Down-regulation of ZC4H2 might affect neural development by affecting the expression of genes related to oxidative phosphorylation signaling pathway. Conclusions: Down-regulation of genes related to the oxidative phosphorylation pathway might be involved in the pathogenity of the disease. Keywords: Female-restricted Wieacker-Wolff Syndrome (WRWF), Wieacker-Wolff Syndrome (WRWFFR), ZC4H2, Arthrogryposis multiplex congenita (AMC), nonsense mutation Overall design: Comparative gene expression profiling analysis of RNA-seq data for ZC4H2 knockdown neural stem cells (NSCs).ENAwith congenital contractures and low fingertip arches, Materials, X-linked, female human body, protein complex, with congenital contractures and muscle atrophy, Proteins, mental retardation, Gm372, mKIAA1166, syndromic 4, Gene, protein, function, protein-containing complex, Apraxia, Wieacker-Wolff Syndrome., Cistrons, female, X-linked recessive, Miles-Carpenter x-linked mental retardation syndrome, WRWFXLR, Wieacker Wolff syndrome, protein polypeptide chains, hca127, native protein, natural protein, polypeptide chain, Contractures of feet, Protein, Gene Products, Genetic Materials, intellectual disability-developmental delay-contractures syndrome, Miles-CARPENTER X-linked mental retardation syndrome, MRXS4, protein aggregate, Wieacker-Wolff syndrome, Genetic Material, contractures of feet, WRWF, with Congenital Contractures and Low Fingertip Arches, X-Linked, Mental Retardation, Genetic, Mental retardation, proteins, INSDC_feature:gene, Miles-Carpenter type, loss of, Protein Gene Products, Gene Proteins, Phenotypes, Miles-Carpenter syndrome, oculomotor, Material, KIAA1166, X-linked intellectual disability, WWS, Cistron, and oculomotor apraxia, foot contractures-muscle atrophy-oculomotor apraxia syndrome, Wieacker syndrome, with congenital contractures and Low fingertip arches, HCA127, muscle atrophy, Severe, Females, MCS, apraxiawith congenital contractures and low fingertip arches, Materials, X-linked, female human body, protein complex, with congenital contractures and muscle atrophy, Proteins, mental retardation, Gm372, mKIAA1166, syndromic 4, Gene, protein, function, protein-containing complex, Apraxia, Wieacker-Wolff Syndrome., Cistrons, female, X-linked recessive, Miles-Carpenter x-linked mental retardation syndrome, WRWFXLR, Wieacker Wolff syndrome, protein polypeptide chains, hca127, native protein, natural protein, polypeptide chain, Contractures of feet, Protein, Gene Products, Genetic Materials, intellectual disability-developmental delay-contractures syndrome, Miles-CARPENTER X-linked mental retardation syndrome, MRXS4, protein aggregate, Wieacker-Wolff syndrome, Genetic Material, contractures of feet, WRWF, with Congenital Contractures and Low Fingertip Arches, X-Linked, Mental Retardation, Genetic, Mental retardation, proteins, INSDC_feature:gene, Miles-Carpenter type, loss of, Protein Gene Products, Gene Proteins, Phenotypes, Miles-Carpenter syndrome, oculomotor, Material, KIAA1166, X-linked intellectual disability, WWS, Cistron, and oculomotor apraxia, foot contractures-muscle atrophy-oculomotor apraxia syndrome, Wieacker syndrome, with congenital contractures and Low fingertip arches, HCA127, muscle atrophy, Severe, Females, MCS, apraxiafalseLoss of protein function of ZC4H2 gene causing severe phenotypes of female-restricted Wieacker Wolff SyndromeLoss of protein function of ZC4H2 gene causing severe phenotypes of female-restricted Wieacker Wolff Syndrome2025-09-242022-07-18PRJNA858652GSE2081719606