A boy presented at age 2.5 years with mild left ventricular hypertrophy and mi ld myopathy. Hypertrophic cardiomyopathy progressed relentlessly, leading to dea th at age 16 years shortly before planned heart transplan...A boy presented at age 2.5 years with mild left ventricular hypertrophy and mi ld myopathy. Hypertrophic cardiomyopathy progressed relentlessly, leading to dea th at age 16 years shortly before planned heart transplantation. During the cour se of the disease, his mother developed severe dilated cardiomyopathy and died o f its complications at 46 years of age. The combination of myopathy and cardiomy opathy, the biochemical and electron microscopy findings in a muscle biopsy, and the pedigree suggested Danon disease (MIM 300257), an X-linked lysosomal stora ge disorder caused by deficiency of lysosome associated membrane protein-2 (LAM P2). The diagnosis was confirmed by the identification of a novel mutation, G138 A, in the LAMP2gene, leading to the premature stop codon W46X. Conclusion:Early diagnosis of Danon disease is important for genetic counselling and timely cardi ac transplantation, the only effective therapeutic option.展开更多
目的以一个临床表型为低血磷性佝偻病(hypophosphatemic rickets,HR)的家系为研究对象,通过全外显子组测序寻找该家系的致病变异基因,并分析变异的致病性。方法收集HR家系临床资料,进行生化检测。提取先证者DNA,进行临床全外显子组测序...目的以一个临床表型为低血磷性佝偻病(hypophosphatemic rickets,HR)的家系为研究对象,通过全外显子组测序寻找该家系的致病变异基因,并分析变异的致病性。方法收集HR家系临床资料,进行生化检测。提取先证者DNA,进行临床全外显子组测序,并针对可疑致病变异对家系所有成员进行PCR扩增,Sanger测序验证。预测变异的致病性及对蛋白质空间结构的影响。结果该家系共3代,先证者是一位26岁女性,先证者母亲、先证者及其儿子和女儿为患者,临床表现为O型腿、鸡胸、低磷血症,骨骼X线检查、生化检测、成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)检测结果提示低血磷性佝偻病。临床全外显子组测序发现PHEX(NM_000444)c.2193dupT的插入移码杂合变异,该变异可导致编码第732位的天冬酰胺变异为终止密码子(p.N732*),从而出现了蛋白质截短。先证者的母亲、儿子及女儿PHEX基因均存在该变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)对变异的分类标准,分级为可能致病性变异。经查阅文献及查找人类基因突变数据库,该变异均未被报道或收录。结论本研究发现了一个PHEX新致病变异,为该家系的临床诊断和治疗及遗传咨询提供了实验依据。展开更多
文摘A boy presented at age 2.5 years with mild left ventricular hypertrophy and mi ld myopathy. Hypertrophic cardiomyopathy progressed relentlessly, leading to dea th at age 16 years shortly before planned heart transplantation. During the cour se of the disease, his mother developed severe dilated cardiomyopathy and died o f its complications at 46 years of age. The combination of myopathy and cardiomy opathy, the biochemical and electron microscopy findings in a muscle biopsy, and the pedigree suggested Danon disease (MIM 300257), an X-linked lysosomal stora ge disorder caused by deficiency of lysosome associated membrane protein-2 (LAM P2). The diagnosis was confirmed by the identification of a novel mutation, G138 A, in the LAMP2gene, leading to the premature stop codon W46X. Conclusion:Early diagnosis of Danon disease is important for genetic counselling and timely cardi ac transplantation, the only effective therapeutic option.
文摘目的以一个临床表型为低血磷性佝偻病(hypophosphatemic rickets,HR)的家系为研究对象,通过全外显子组测序寻找该家系的致病变异基因,并分析变异的致病性。方法收集HR家系临床资料,进行生化检测。提取先证者DNA,进行临床全外显子组测序,并针对可疑致病变异对家系所有成员进行PCR扩增,Sanger测序验证。预测变异的致病性及对蛋白质空间结构的影响。结果该家系共3代,先证者是一位26岁女性,先证者母亲、先证者及其儿子和女儿为患者,临床表现为O型腿、鸡胸、低磷血症,骨骼X线检查、生化检测、成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)检测结果提示低血磷性佝偻病。临床全外显子组测序发现PHEX(NM_000444)c.2193dupT的插入移码杂合变异,该变异可导致编码第732位的天冬酰胺变异为终止密码子(p.N732*),从而出现了蛋白质截短。先证者的母亲、儿子及女儿PHEX基因均存在该变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)对变异的分类标准,分级为可能致病性变异。经查阅文献及查找人类基因突变数据库,该变异均未被报道或收录。结论本研究发现了一个PHEX新致病变异,为该家系的临床诊断和治疗及遗传咨询提供了实验依据。
