A novel nonsense heterozygous mutation (p.R67X; c.199C>T) in the ZC4H2 gene was identified in a female patient with Wieacker-Wolff syndrome, resulting in a truncated protein.
Case Report (n=1)
A novel de novo nonsense mutation in ZC4H2 (p.R67X) is implicated in the pathogenesis of Wieacker-Wolff syndrome in a female patient.
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.
Wang et al. (Mon,) conducted a case report in Wieacker-Wolff syndrome (n=1). ZC4H2 gene nonsense heterozygous mutation (p.R67X; c.199C>T) was evaluated on Identification of genetic mutation and its effects. A novel nonsense heterozygous mutation (p.R67X; c.199C>T) in the ZC4H2 gene was identified in a female patient with Wieacker-Wolff syndrome, resulting in a truncated protein.
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