To the Editor:Cervical cancer(CC)is the second leading cause of cancer death in women,representing a major global health challenge.[1]Cervical squamous cell carcinoma(CSCC)accounts for 70%of CC cases,and pelvic lymph ...To the Editor:Cervical cancer(CC)is the second leading cause of cancer death in women,representing a major global health challenge.[1]Cervical squamous cell carcinoma(CSCC)accounts for 70%of CC cases,and pelvic lymph node metastasis is a critical cause of CC-related death.[2]Thus,understanding the underlying mechanisms of the tumor spread through lymphatic vessels becomes imperative.[3]RNA helicases are involved in almost all aspects of RNA metabolism.[4]DEAD-box helicase 24(DDX24),one of the least explored DEAD-box RNA helicases,was upregulated in several cancer types.[5]However,the role of DDX24 in CSCC progression and metastasis remains elusive.Here,we investigated the essential role of DDX24 in mediating cancer cell EMT and lymphangiogenesis in the context of CSCC.Our study provides a potential therapeutic target for CSCC lymphatic metastasis.展开更多
Background： Congenital myasthenic syndromes （CMSs） are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS th...Background： Congenital myasthenic syndromes （CMSs） are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation （c.5302G〉C） of AGRN in a Chinese CMS pedigree. Methods： We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease-related gene panel containing 519 genes associated with genetic myopathy （including 17 CMS genes）. Results： In the family, the proband showed limb-girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband＇s two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation （c.5302G〉C, p.A1768P） of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. Conclusions： This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb-girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.展开更多
基金National Natural Science Foundation of China(Nos.92159105 and 81872113)Guangdong Province(No.2020A0505100028)
文摘To the Editor:Cervical cancer(CC)is the second leading cause of cancer death in women,representing a major global health challenge.[1]Cervical squamous cell carcinoma(CSCC)accounts for 70%of CC cases,and pelvic lymph node metastasis is a critical cause of CC-related death.[2]Thus,understanding the underlying mechanisms of the tumor spread through lymphatic vessels becomes imperative.[3]RNA helicases are involved in almost all aspects of RNA metabolism.[4]DEAD-box helicase 24(DDX24),one of the least explored DEAD-box RNA helicases,was upregulated in several cancer types.[5]However,the role of DDX24 in CSCC progression and metastasis remains elusive.Here,we investigated the essential role of DDX24 in mediating cancer cell EMT and lymphangiogenesis in the context of CSCC.Our study provides a potential therapeutic target for CSCC lymphatic metastasis.
文摘Background： Congenital myasthenic syndromes （CMSs） are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation （c.5302G〉C） of AGRN in a Chinese CMS pedigree. Methods： We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease-related gene panel containing 519 genes associated with genetic myopathy （including 17 CMS genes）. Results： In the family, the proband showed limb-girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband＇s two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation （c.5302G〉C, p.A1768P） of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. Conclusions： This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb-girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.
