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Background Wieacker‐Wolff syndrome (WWS) is a congenital X‐linked neuromuscular disorder, which was firstly reported in 1985. Zinc finger C4H2‐type containing (ZC4H2) gene has been found to be associated with the disease pathogenesis. However, the underlying mechanism remains elusive. Methods Whole‐exome sequencing was performed to identify the mutations. Expression plasmids were constructed and cell culture and immune‐biochemical assays were used to examine the effects of the mutation. Results We reported a female patient with classical symptoms of WWS and discovered a novel nonsense heterozygous mutation (p.R67X; c.199C>T) in ZC4H2 gene in the patient but not in her parents. The mutation resulted in a 66 amino‐acid truncated ZC4H2 protein. The mutation is located in the key helix domain and it altered the subcellular locations of the mutant ZC4H2 protein. X‐chromosome inactivation (XCI) pattern analysis revealed that the XCI ratio of the proband was 22:78. Conclusion Female heterozygous carriers with nonsense mutation with a truncated ZC4H2 protein could lead to the pathogenesis of Wieacker‐Wolff syndrome and our study provides a potential new target for the disease treatment.

BackgroundCross protection is a promising alternative to control plant viral diseases. One critical factor limiting the application of cross protection is the availability of attenuated mutants or mild strains. Potato virus X (PVX) infects many crops and induces huge economic losses to agricultural production. However, researches on the variability and mechanism of PVX virulence are scarce.MethodsThe mutants were obtained by introducing mutations into the RNA dependent RNA polymerase (RdRp) gene of PVX via site-directed mutagenesis. Attenuated mutants were screen according to their symptoms in Nicotiana benthamiana plants. The protection efficacy against severe infection were evaluated with interval of 5, 10 and 15 days.ResultsAmong the 40 mutants obtained, four mutants carrying substitutions of either Glu46, Asn863, Asn968 or Glu1001 to Ala in PVX RdRp showed drastically attenuated symptom, accompanying with reduced accumulation levels of coat protein, plus- and minus-sense RNAs. When the interval between protective and challenging inoculations was 15 days, mutant E1001A (with substitution of Glu1001 to Ala in RdRp) provided complete protection against severe infection in both Nicotiana benthamiana and tomato, while E46A (Glu46 mutated to Ala) provided incomplete protection. To reduce the risk of reverse mutation, we constructed mutant dM which carries double mutations of both Glu46 and Glu1001 to Ala in RdRp. The mutant dM could provide effective protection against severe PVX infection.ConclusionMutations of Glu46, Asn863, Asn968 or Glu1001 to Ala in PVX RdRp significantly reduced the viral symptoms. Mutants E1001A and E46A could provide effective protection against wild type PVX in both Nicotiana benthamiana and tomato. These results provide theoretical and practical bases for the control of PVX via cross protection.