293T cells Transcriptome

Female-restricted Wieacker Wolff syndrome (WRWFFR) are a group of genetic diseases caused by variants of ZC4H2 on the X chromosome. 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. To investigate the association between a de novo c.352C>T mutation in ZC4H2 (NM_ 018684.4) and WRWFFR, as well as explore the potential mechanisms.A female neonate, born with severe AMC and Pierre-Robin sequence (cleft palate and micrognathia), was found to carry a de novo nonsense heterozygous mutation c.352C>T (p.Gln118*) of ZC4H2. RT-qPCR analysis revealed no significant differences in the mRNA expression of ZC4H2 compared between the MT and WT groups. ZC4H2 protein could be detected in the WT group, whereas the truncated ZC4H2 protein could not do so in the MT group. The RNA seq results revealed that the expression pattern in the MT group differed significantly from that in the WT group. Finally, KEGG analysis revealed that a series of genes involved in the oxidative phosphorylation pathway were down expressed in the MT group. ZC4H2 c.352C>T(p.Gln118*) mutation was shown to result in loss of protein function, which may be the causative factor of WRWFFR.