http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
He Liting,Wang Yao,Pan Jiahua,Guo Limin,Zhou Haoquan,Zhang Lan 한국유전학회 2024 Genes & Genomics Vol.46 No.4
Background Neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies (NEDDFSA) is a rare and phenotypically variable disorder. The zinc finger MIZ-type containing 1 gene (ZMIZ1) is a causative gene of NEDDFSA that encodes a protein inhibitor of the activated STAT-like family transcriptional regulator. Given the rarity of reported NEDDFSA cases, new phenotypes and genotypes of this disorder are still being discovered. Objective This study describes the phenotype characteristics of a Chinese NEDDFSA family caused by a novel ZMIZ1 variant. Methods We reviewed the clinical phenotype of a Chinese patient with NEDDFSA and performed whole-exome sequencing (WES) of the patient’s family. We simulated the potential biological harmfulness of the mutant protein. Plasmids were constructed and used for western blot and immunofluorescence assays to analyze protein expression levels. Results The patient was a 6-month-old male infant who exhibited dysmorphic facial features, neurodevelopmental abnormalities, congenital heart disease, and previously unreported genitourinary system anomalies. WES revealed a non-frameshift deletion variant in ZMIZ1 (NM_020338.4: c.858_875del, p.Val288_Ala293del), resulting in a structural alteration in the protein’s alanine-rich domain. Western blot and immunofluorescence assays indicated a significant decrease in the expression level of the mutant ZMIZ1 protein compared to the wild-type protein. Conclusion The clinical manifestations of this patient may be associated with the ZMIZ1 variant, and the structural alteration in the alanine-rich domain of the ZMIZ1 protein may contribute to a more complex disease phenotype. These results expand the genotype–phenotype correlation of ZMIZ1. Background Neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies (NEDDFSA) is a rare and phenotypically variable disorder. The zinc finger MIZ-type containing 1 gene (ZMIZ1) is a causative gene of NEDDFSA that encodes a protein inhibitor of the activated STAT-like family transcriptional regulator. Given the rarity of reported NEDDFSA cases, new phenotypes and genotypes of this disorder are still being discovered. Objective This study describes the phenotype characteristics of a Chinese NEDDFSA family caused by a novel ZMIZ1 variant. Methods We reviewed the clinical phenotype of a Chinese patient with NEDDFSA and performed whole-exome sequencing (WES) of the patient’s family. We simulated the potential biological harmfulness of the mutant protein. Plasmids were constructed and used for western blot and immunofluorescence assays to analyze protein expression levels. Results The patient was a 6-month-old male infant who exhibited dysmorphic facial features, neurodevelopmental abnormalities, congenital heart disease, and previously unreported genitourinary system anomalies. WES revealed a non-frameshift deletion variant in ZMIZ1 (NM_020338.4: c.858_875del, p.Val288_Ala293del), resulting in a structural alteration in the protein’s alanine-rich domain. Western blot and immunofluorescence assays indicated a significant decrease in the expression level of the mutant ZMIZ1 protein compared to the wild-type protein. Conclusion The clinical manifestations of this patient may be associated with the ZMIZ1 variant, and the structural alteration in the alanine-rich domain of the ZMIZ1 protein may contribute to a more complex disease phenotype. These results expand the genotype–phenotype correlation of ZMIZ1.
Shushu Wang,Dongyao Wang,Xuesong Wang,Mingwu Chen,Yanshi Wang,Haoquan Zhou,Yonggang Zhou,Yong Lv,Haiming Wei The Korean Association of Immunobiologists 2024 Immune Network Vol.24 No.2
Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients' CD4<sup>+</sup> T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4<sup>+</sup> T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.