Objective:To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN).Methods:A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion:The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

AIM:To explore the effect of microRNA-184(miR-184)on compensatory lung growth(CLG)af-ter lobectomy in multiple primary lung cancer(MPLC)and its mechanism.METHODS:(1)Lung tissue samples(n= 16)from MPLC patients and patients with good recovery after lobectomy(CLG)were collected,and the expression of miR-184 was measured by RT-qPCR.(2)Human alveolar epithelial cells were divided into NC-mimic group,miR-184 mimic group,OE-NC group,tissue inhibitor of metalloproteinase-2(TIMP-2)overexpression(OE-TIMP-2)group,and miR-184 mimic+OE-TIMP-2 group according to the transfection(n=3).The expression of miR-184,TIMP-2 mRNA and matrix metalloproteinase-14(MMP-14)mRNA was measured by RT-qPCR,and the protein expression of TIMP-2 and MMP-14 was determined by Western blot.The proliferation of the cells was measured by CCK-8 and colony formation assays.(3)C57BL/6J mice were divided into pneumonectomy(PNX)group and PNX+miR-184 mimic group(n=5).The flexiVent system was used to measure the vital capacity and lung compliance of the mice.Lung volume was measured by water dis-placement method,and lung tissue changes were observed by HE staining.RESULTS:The expression of miR-184 was significantly higher in the patients with better recovery after lobectomy(P＜0.01).Overexpression of miR-184 promoted the proliferation of human alveolar epithelial cells and the recovery of lung function in mice after PNX.In terms of mecha-nism,miR-184 showed targeted binding with TIMP-2,and overexpression of miR-184 promoted the expression of MMP-14 by inhibiting TIMP-2,thereby promoting the proliferation of human alveolar epithelial cells and the recovery of mouse lung function after PNX.CONCLUSION:miR-184 promotes CLG after PNX through the TIMP-2/MMP-14 axis.

BACKGROUND: m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer and regulates tumor immunity. Current studies mostly focus on the differential expression of some specific m6A effectors and infiltrating immune cell. m6A methylation modification is the result of mutual adjustment and balance between effectors, and changes in the expression of one or two effectors are far from enough to reflect the panorama of m6A methylation. The role of m6A in the immune microenvironment of lung adenocarcinoma (LUAD) is still poorly understood. The aim of this study is to investigate the effect of different m6A modification patterns in immune microenvironment of LUAD. METHODS: LUAD data was obtained from The Cancer Genome Atlas (TCGA), University of California Santa Cruz Xena (UCSC Xena) and Gene Expression Omnibus (GEO) databases. Gene mutation, differential expression and survival analysis were performed for 24 m6A effectors. The m6A modification pattern was constructed by unsupervised clustering method, and the m6A clusters survival analysis, gene set variation analysis, immune score and immune cell infiltration analysis were performed. The association between LRPPRC protein expression levels and infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages in the tumor microenvironment was validated by immunohistochemistry in LUAD tissue microarray with 68 cases. RESULTS: The mutations of m6A effector were found in 150 of 567 LUAD cases with a frequency of 26.46%. 6 readers and 3 writers were significantly up regulated in LUAD tissues compared with normal tissues. IGF2BP1 and HNRNPC are the independent risk factors for prognosis of LUAD. Abundant cross-talks among writers, erasers and readers were demonstrated. Three m6A modification patterns with different immune cell infiltration characteristics and clinical prognosis were established. Among m6A effectors, LRPPRC was found to be inversely associated with the infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages, and was validated in 68 LUAD tissues. CONCLUSIONS m6A modification patterns play non-negligible roles in regulating the immune microenvironment. LRPPRC has potential to be a new biomarker for checkpoint inhibitor immunotherapy.
Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/pathology* ; Adenosine/metabolism* ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/pathology* ; Methylation ; Tumor Microenvironment/genetics*