BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the ...BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.展开更多
目的探讨LAMA4调控TGF-β1/SMAD Western blot检测LAMA4在肝癌细胞Huh7和HepG2及正常肝细胞L02中的表达;MMT法和流式细胞技术检测LAMA4和TGF-β1/SMAD信号传导途径对Huh7细胞增殖和凋亡的影响;RT-qPCR和Western blot检测LAMA4对TGF-β1/...目的探讨LAMA4调控TGF-β1/SMAD Western blot检测LAMA4在肝癌细胞Huh7和HepG2及正常肝细胞L02中的表达;MMT法和流式细胞技术检测LAMA4和TGF-β1/SMAD信号传导途径对Huh7细胞增殖和凋亡的影响;RT-qPCR和Western blot检测LAMA4对TGF-β1/SMAD信号转导通路和细胞免疫因子TNF-α、IFN-γ、TGF-β1的影响。结果 RT-qPCR和Western blot检测结果显示:LAMA4在肝癌细胞Huh7和HepG2中mRNA表达显著上调;LAMA4在肝癌细胞Huh7和HepG2中蛋白表达显著上调;沉默LAMA4使TGF-β1和SMAD4表达显著上调,SMAD6、IFN-γ和TNF-α的含量显著降低,过表达LAMA4则结果相反;MMT法和流式细胞技术检测结果显示:敲低LAMA4可使Huh7细胞活力下降,细胞凋亡率增加,而过表达LAMA4则结果相反;Ly364947干扰TGF-β1/SMAD信号传导路径后,Huh7细胞的活力增加,细胞凋亡率显著下降,IFN-γ和TNF-α的含量显著升高,TGF-β1显著降低,且Ly364947可部分逆转沉默LAMA4对肝癌细胞Huh7的免疫逃逸因子和凋亡的调控作用。结论 LAMA4可通过调控TGF-β1/SMAD信号传导途径影响肝癌细胞免疫逃逸和凋亡。展开更多
基金Supported by The Suzhou Science and Technology Development Plan Guiding Project,No.SZSYYXH-2023-YB5The Suzhou Science and Technology Development Plan Project,No.SKY2023002The Suzhou Key Laboratory of Children's Structural Deformities,No.SZS2022018.
文摘BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.
