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
One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a...One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a defective mineralization of bones and also affects the growth in children. Clinical diagnosis should be suspected in children with signs of rickets and hypophosphatemia with normal calcium levels. We describe clinical characteristics and genetic results of four patients diagnosed and treated in our Nephrology Section. All patients have a “de novo” XHR as none familiars are affected. Early diagnosis should be suspected before the bone deformities have been submitted and the growth would have been impaired.展开更多
X-连锁低血磷性佝偻病(X-linked hypophosphatemic rickets,XLH)是伴X染色体显性遗传的罕见病。其临床表型差异较大,即使是同一个家系,临床表现的轻重也有所差异。这可能与位于X染色体上与内肽酶同源的磷酸盐调节基因(phosphate-regulat...X-连锁低血磷性佝偻病(X-linked hypophosphatemic rickets,XLH)是伴X染色体显性遗传的罕见病。其临床表型差异较大,即使是同一个家系,临床表现的轻重也有所差异。这可能与位于X染色体上与内肽酶同源的磷酸盐调节基因(phosphate-regulating gene with homologies to endopeptidases on X chromosome,PHEX)突变有关。本文从PHEX基因的突变类型、突变位点以及突变剂量方面,对XLH基因型和临床表型的相关性予以综述,以期为XLH的基因研究与早期临床诊疗提供依据。展开更多
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。
文摘One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a defective mineralization of bones and also affects the growth in children. Clinical diagnosis should be suspected in children with signs of rickets and hypophosphatemia with normal calcium levels. We describe clinical characteristics and genetic results of four patients diagnosed and treated in our Nephrology Section. All patients have a “de novo” XHR as none familiars are affected. Early diagnosis should be suspected before the bone deformities have been submitted and the growth would have been impaired.
文摘X-连锁低血磷性佝偻病(X-linked hypophosphatemic rickets,XLH)是伴X染色体显性遗传的罕见病。其临床表型差异较大,即使是同一个家系,临床表现的轻重也有所差异。这可能与位于X染色体上与内肽酶同源的磷酸盐调节基因(phosphate-regulating gene with homologies to endopeptidases on X chromosome,PHEX)突变有关。本文从PHEX基因的突变类型、突变位点以及突变剂量方面,对XLH基因型和临床表型的相关性予以综述,以期为XLH的基因研究与早期临床诊疗提供依据。
