Rhizomelic Chondrodysplasia Punctata Type I is one of the rare peroxisome disorders. We report the case of a newborn white male that developed seizures and skeletal dysmorphism. The baby had short humerus bones with s...Rhizomelic Chondrodysplasia Punctata Type I is one of the rare peroxisome disorders. We report the case of a newborn white male that developed seizures and skeletal dysmorphism. The baby had short humerus bones with stippled epiphy-ses, consistent with the disease. He had also delay in myelinization on brain MRI with bilateral subependymal cysts over the atria and frontal horns of the lateral ventricles. Usually, infants with this disorder do not live long. This unfor-tunate little patient died at 5 weeks age from pneumonia. We emphasize the importance of antenatal screening for these disorders especially when a family history of dysmorphism is positive.展开更多
Although the pathogenesis and mechanism of congenital skeletal dysplasia are bet-ter understood,progress in drug development and intervention research remains limited.Here we report that melatonin treatment elicits a ...Although the pathogenesis and mechanism of congenital skeletal dysplasia are bet-ter understood,progress in drug development and intervention research remains limited.Here we report that melatonin treatment elicits a mitigating effect on skeletal abnormalities caused by SLC26A2 deficiency.In addition to our previous finding of endoplasmic reticulum stress upon SLC26A2 deficiency,we found calcium(Ca^(2+))overload jointly contributed to SLC26A2-associ-ated chondrodysplasias.Continuous endoplasmic reticulum stress and cytosolic Ca^(2+)overload in turn triggered apoptosis of growth plate chondrocytes.Melatonin,known for its anti-oxidant and anti-inflammatory properties,emerged as a promising therapeutic approach in our study,which enhanced survival,proliferation,and maturation of chondrocytes by attenuating endo-plasmic reticulum stress and Ca^(2+)overload.Our findings not only demonstrated the efficacy of melatonin in ameliorating abnormal function and cell fate of SLC26A2-deficient chondrocytes in vitro but also underscored its role in partially alleviating the skeletal dysplasia seen in Col2a1-CreERT2;slc26a2f/n mice.As revealed by histology and micro-CT analyses,melatonin significantly improved retarded cartilage growth,defective trabecular bone formation,and tibial genu varum in vivo.Collectively,these data shed translational insights for drug development and support melatonin as a potential treatment for SLC26A2-related chondrodysplasias.展开更多
目的对2021年1月陆军军医大学第二附属医院接诊的1例Schmid型干骺端软骨发育不全(Schmid type metaphyseal chondrodysplasia,SMCD)家系进行疾病表型与基因型分析,结合文献复习探讨其防治手段。方法对先证者进行家系调查及系谱分析,收...目的对2021年1月陆军军医大学第二附属医院接诊的1例Schmid型干骺端软骨发育不全(Schmid type metaphyseal chondrodysplasia,SMCD)家系进行疾病表型与基因型分析,结合文献复习探讨其防治手段。方法对先证者进行家系调查及系谱分析,收集先证者及家系成员的临床资料,采用全外显子组测序明确突变基因,并通过Sanger测序验证和家系共分离分析,同时结合ACMG指南进行生物信息学分析来评价变异的致病性。结果在家系患者中发现COL10A1基因存在新的杂合错义突变c.1843T>G(p.Tyr615Asp),该位点所在区域在不同物种之间高度保守,此突变可能通过影响X型胶原(α1)蛋白的三聚化及其与细胞外基质分子结合导致疾病发生。结论发现了1种SMCD的新突变,丰富了SMCD患者的突变谱,为SMCD的预防、诊断及治疗提供理论依据。展开更多
文摘Rhizomelic Chondrodysplasia Punctata Type I is one of the rare peroxisome disorders. We report the case of a newborn white male that developed seizures and skeletal dysmorphism. The baby had short humerus bones with stippled epiphy-ses, consistent with the disease. He had also delay in myelinization on brain MRI with bilateral subependymal cysts over the atria and frontal horns of the lateral ventricles. Usually, infants with this disorder do not live long. This unfor-tunate little patient died at 5 weeks age from pneumonia. We emphasize the importance of antenatal screening for these disorders especially when a family history of dysmorphism is positive.
基金supported by the National Natural Science Foundation of China (No.82272442,82372361)the Key Industrial Chain Program of Shaanxi,China (No.2022ZDLSF02-12).
文摘Although the pathogenesis and mechanism of congenital skeletal dysplasia are bet-ter understood,progress in drug development and intervention research remains limited.Here we report that melatonin treatment elicits a mitigating effect on skeletal abnormalities caused by SLC26A2 deficiency.In addition to our previous finding of endoplasmic reticulum stress upon SLC26A2 deficiency,we found calcium(Ca^(2+))overload jointly contributed to SLC26A2-associ-ated chondrodysplasias.Continuous endoplasmic reticulum stress and cytosolic Ca^(2+)overload in turn triggered apoptosis of growth plate chondrocytes.Melatonin,known for its anti-oxidant and anti-inflammatory properties,emerged as a promising therapeutic approach in our study,which enhanced survival,proliferation,and maturation of chondrocytes by attenuating endo-plasmic reticulum stress and Ca^(2+)overload.Our findings not only demonstrated the efficacy of melatonin in ameliorating abnormal function and cell fate of SLC26A2-deficient chondrocytes in vitro but also underscored its role in partially alleviating the skeletal dysplasia seen in Col2a1-CreERT2;slc26a2f/n mice.As revealed by histology and micro-CT analyses,melatonin significantly improved retarded cartilage growth,defective trabecular bone formation,and tibial genu varum in vivo.Collectively,these data shed translational insights for drug development and support melatonin as a potential treatment for SLC26A2-related chondrodysplasias.
文摘目的对2021年1月陆军军医大学第二附属医院接诊的1例Schmid型干骺端软骨发育不全(Schmid type metaphyseal chondrodysplasia,SMCD)家系进行疾病表型与基因型分析,结合文献复习探讨其防治手段。方法对先证者进行家系调查及系谱分析,收集先证者及家系成员的临床资料,采用全外显子组测序明确突变基因,并通过Sanger测序验证和家系共分离分析,同时结合ACMG指南进行生物信息学分析来评价变异的致病性。结果在家系患者中发现COL10A1基因存在新的杂合错义突变c.1843T>G(p.Tyr615Asp),该位点所在区域在不同物种之间高度保守,此突变可能通过影响X型胶原(α1)蛋白的三聚化及其与细胞外基质分子结合导致疾病发生。结论发现了1种SMCD的新突变,丰富了SMCD患者的突变谱,为SMCD的预防、诊断及治疗提供理论依据。
