OBJECTIVE: To investigate the expression and significance of miRNA-324-3p and its target gene WNT2B in tissue specimens of nasopharyngeal carcinoma (NPC) specimens. METHOD: qRT-PCR was used to detect the expression of miRNA-324-3p and WNT2B mRNA, and Western blot was applied to assay the expression of WNT2B protein in 39 cases of NPC specimens and 21 cases of non-carcinoma epithelium. The relationship between their expression levels and clinicopathological characteristics and their correlation with clinical pathological parameters was analyzed. RESULT: The expression of miRNA-324-3p was significantly down-regulated decreased but WNT2B mRNA/protein increased obviously in NPC specimens (P < 0.01). A negative correlation between miRNA-324-3p and WNT2B was spotted (P < 0.05). The expression levels of these markers were closely correlated with T stage, clinic stage and cervical lymph node metastasis (P < 0.05). CONCLUSION The loss of miRNA-324-3p and ectopic WNT2B might co-induce the initiation and progression of NPC.
Carcinoma ; Glycoproteins ; genetics ; metabolism ; Humans ; Lymphatic Metastasis ; MicroRNAs ; metabolism ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; metabolism ; Neoplasm Proteins ; metabolism ; RNA, Messenger ; metabolism ; Wnt Proteins ; genetics ; metabolism

OBJECTIVE: To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. METHODS: A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. RESULTS: WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3). CONCLUSION The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Male ; Pregnancy ; Exons ; Intellectual Disability/genetics* ; Mothers ; Mutation ; p21-Activated Kinases/genetics* ; Parents ; RNA Splicing

Objective:To explore the genetic etiology of a child with primary hypertrophic osteoarthropathy(PHO).Methods:A child who was admitted to Zhongnan Hospital of Wuhan University on July 27, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing. Suspected splicing variant was verified by Sanger sequencing of family members. In vitro function was validated through a minigene assay, whilst the suspected exonic deletion was validated by long-fragment PCR. This study was approved by the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-011). Results:Whole exome sequencing revealed that the child has harbored compound heterozygous variants of HPGD gene, including a heterozygous deletion (Exon 3 del) derived from his father and a splicing variant (c.421+ 1G>T) derived from his mother. Long-fragment PCR verified that the child and his father had both harbored a 7 565 bp heterozygous deletion (c.218-1304_324+ 6156del), whilst the minigene assay proved that the splicing variant has resulted in skipping of exon 4. Conclusion:The heterozygous c. 218-1304_324+ 6156del deletion and the c. 421+ 1G>T splicing variant of the HPGD gene probably underlay the pathogenesis in this child. Above finding has enriched the mutational spectrum of the HPGD gene and provided a basis for genetic counseling and prenatal diagnosis for this family.