BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There ...BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There are few case reports and genetic analyses,especially of KDM6A gene mutation,in China.CASE SUMMARY This study reports a de novo KDM6A mutation in a Chinese infant with KS.A 2-month-old Chinese baby was diagnosed with KS,which manifested as hypoglycemia,congenital anal atresia at birth,feeding difficulties,hypotonia,and serious postnatal growth retardation.He died of recurrent respiratory infections at age 13 mo.DNA sequencing of his blood DNA revealed a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19).CONCLUSION We present a Chinese KS patient with a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19),broadening the mutation spectrum.展开更多
目的探讨KDM6A突变或表达与胃癌临床病理特征的关系及其对胃癌患者预后的影响。方法通过二代测序对57例胃癌组织进行全外显子测序,以及Cbioportal、Kaplan Meier-Plotter和the Human Protein Atlas等生物信息数据库资料,分析KDM6A突变...目的探讨KDM6A突变或表达与胃癌临床病理特征的关系及其对胃癌患者预后的影响。方法通过二代测序对57例胃癌组织进行全外显子测序,以及Cbioportal、Kaplan Meier-Plotter和the Human Protein Atlas等生物信息数据库资料,分析KDM6A突变与胃癌临床病理特征和胃癌患者总生存时间的关系。结果57例胃癌样本中,KDM6A突变14例,突变率为24.6%。突变组与未突变组比较,Borrmann分型、T分期、TNM分期和肿瘤直径差异有统计学意义(均P<0.05),突变组患者的中位生存时间(53.5个月)短于未突变组(72.0个月,P=0.007)。Kaplan Meier-Plotter数据库的875例胃癌患者中,KDM6A低表达者655例,高表达者220例,低表达患者的中位生存时间(23.5个月)短于高表达患者(30.8个月,P=0.002)。在男性、Ⅲ期、肠型、弥漫型、单纯手术治疗和含氟尿嘧啶方案化疗的患者中,KDM6A表达与患者的总生存时间有关(均P<0.05)。Cbioportal数据库的1172例胃癌患者中,KDM6A突变者70例,未突变者1100例,突变患者的总生存时间(28.9个月)短于未突变患者(35.9个月,P<0.001)。the Human Protein Atlas数据库的355例胃癌患者中,KDM6A高表达97例,KDM6A低表达258例,低表达患者的中位生存时间(13.7个月)短于高表达患者(19.8个月,P=0.022)。结论KDM6A突变、低表达胃癌患者的生存时间更短,且与临床病理因素相关,有可能成为胃癌诊断及治疗的潜在靶点。展开更多
Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The hi...Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B （also known as JMJD3） was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate （ALP） activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 （osterix, OSX）, as well as extracellular matrix genes BGLAP （osteoclacin, OCN） and SPP1 （osteopontin, OPN）, was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 （BMP2） promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.展开更多
文摘BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There are few case reports and genetic analyses,especially of KDM6A gene mutation,in China.CASE SUMMARY This study reports a de novo KDM6A mutation in a Chinese infant with KS.A 2-month-old Chinese baby was diagnosed with KS,which manifested as hypoglycemia,congenital anal atresia at birth,feeding difficulties,hypotonia,and serious postnatal growth retardation.He died of recurrent respiratory infections at age 13 mo.DNA sequencing of his blood DNA revealed a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19).CONCLUSION We present a Chinese KS patient with a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19),broadening the mutation spectrum.
文摘目的探讨KDM6A突变或表达与胃癌临床病理特征的关系及其对胃癌患者预后的影响。方法通过二代测序对57例胃癌组织进行全外显子测序,以及Cbioportal、Kaplan Meier-Plotter和the Human Protein Atlas等生物信息数据库资料,分析KDM6A突变与胃癌临床病理特征和胃癌患者总生存时间的关系。结果57例胃癌样本中,KDM6A突变14例,突变率为24.6%。突变组与未突变组比较,Borrmann分型、T分期、TNM分期和肿瘤直径差异有统计学意义(均P<0.05),突变组患者的中位生存时间(53.5个月)短于未突变组(72.0个月,P=0.007)。Kaplan Meier-Plotter数据库的875例胃癌患者中,KDM6A低表达者655例,高表达者220例,低表达患者的中位生存时间(23.5个月)短于高表达患者(30.8个月,P=0.002)。在男性、Ⅲ期、肠型、弥漫型、单纯手术治疗和含氟尿嘧啶方案化疗的患者中,KDM6A表达与患者的总生存时间有关(均P<0.05)。Cbioportal数据库的1172例胃癌患者中,KDM6A突变者70例,未突变者1100例,突变患者的总生存时间(28.9个月)短于未突变患者(35.9个月,P<0.001)。the Human Protein Atlas数据库的355例胃癌患者中,KDM6A高表达97例,KDM6A低表达258例,低表达患者的中位生存时间(13.7个月)短于高表达患者(19.8个月,P=0.022)。结论KDM6A突变、低表达胃癌患者的生存时间更短,且与临床病理因素相关,有可能成为胃癌诊断及治疗的潜在靶点。
文摘Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B （also known as JMJD3） was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate （ALP） activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 （osterix, OSX）, as well as extracellular matrix genes BGLAP （osteoclacin, OCN） and SPP1 （osteopontin, OPN）, was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 （BMP2） promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.
