常染色体显性遗传性多囊肾病临床及基因突变分析

目的 分析常染色体显性遗传性多囊肾病（ADPKD）患者临床特征及基因突变特点。方法 入选ADPKD患者23例,收集临床数据,并进行家系调查;抽取外周血经高通量测序方法进行多囊肾基因检测。结果 23例ADPKD患者主要临床表现为腰腹痛、血尿、感染,肾功能不全;与女性患者相比,男性ADPKD患者血尿酸水平明显增高;基因检测PKD1基因突变19例;PKD2基因突变4例。同处于慢性肾脏病（CKD）5期的ADPKD患者,PKD1基因突变患者血红蛋白明显低于PKD2基因突变患者（65.89±13.59 vs 97.5±17.02,P<0.01）。结论 ADPKD可进展至肾功能衰竭,基因检测有助于早期诊断和预后评估,终末期ADPKD患者,PKD1基因突变患者预后更差。     

两个中国常染色体显性遗传性多囊肾病家系的表型与基因型分析

目的研究中国人多囊肾病基因1（polycystic kidney disease 1 gene，PKD1）突变的特点，检测基因突变位点。方法25例多囊肾患者，正常对照16名，扩增PKD1基因的第44、45外显子的基因片段，变性梯度凝胶电泳突变检测系统进行初筛，然后测序。结果发现1个移码突变（12431delCT）、1个无义突变（C12217T）、1个多态性（A50747C），突变检测率为8％（2／25）。结论检测到2个新的可能的致病突变：1个移码突变（12431delCT）、1个无义突变（C12217T）。     

多囊肾病的临床实践指南

多囊肾病(polycystic kidney disease,PKD)是由基因突变所导致的一类遗传性肾病,按其遗传方式又分为常染色体显性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)和常染色体隐性多囊肾病(autosom al recessive polycystic kidney disease,ARPKD)。该病的主要病理特点是肾脏囊肿进行性增大、增多,破坏正常的肾脏结构,最终导致终末期肾病(end stage renal disease,ESRD),患者只能依靠透析或肾移植维持生命。我们在参考国内外本领域的基础研究、临床研究和相关指南共识的基础上,结合中国人群的实际情况编写了该项指南,旨在总结多囊肾病的医学遗传学知识和临床处置要点,以提高临床医师的认识水平,为该病的诊治提供规范化建议。     

一个可能与PKD2基因连锁的常染色体显性多囊肾病家系

目的 研究常染色体显性多囊肾病（autosomal dominant polycystic kidney disease,ADPKD）在中国人中的遗传异质性。方法 采用聚合酶链反应 （polymerase chain reaction, PCR）、非变性聚丙烯酰胺凝胶电泳,检测了1个ADPKD家系各成员中与PKD1基因连锁的4种和与PKD2连锁的4种微卫星标记的基因分型。然后以软件辅助构建单倍型,并推测疾病单倍型。结果 发现该ADPKD家系中,与PKD1紧密连锁的4个微卫星KG8、SM6、CW4和CW2是有信息的;与PKD2基因紧密连锁的3种微卫星DNAIMS1563、D4S414和D4S423是有信息的。推定的单倍型提示,在这个家系中疾病可能与PKD2连锁,而不与PKD1连锁。结论 在此家系中,受累成员间存在表型异质性,并且有一个早发的儿童患者。与PKD2连锁的家系较少,这个家系的报道表明中国人中存在ADPKD的遗传异质性,PKD2的异常也可能会引起中国人ADPKD的发生。另外,发现有遗传早现现象存在,且疾病通过母亲传递。这提示在与PKD1不连锁的家系中后代可能早发病。     

常染色体隐性遗传视网膜色素变性的相关基因研究进展

视网膜色素变性（retinitis pigmentosa,RP)是一组进行性的可致盲的单基因遗传性视网膜疾病，以视网膜光感受器和色素上皮功能进行性受损为主要特征。常染色体隐性视网膜色素变性（autosoma recessive RP,adRP)属视网膜色素变性的一种类型，具有遗传异质性和临床异质性。目前巳克隆了15个致病基因，包括PDEA、PDEB、CNGA1、ABCA4、RLBP1、RPE65、TULP1和CRB1等。现简介绍下。     

一例常染色体隐性多囊肾病家系 PKHD1基因变异分析

目的对1例常染色体隐性多囊肾病胎儿的PKHD1基因进行变异分析, 明确其致病原因。方法收集引产胎儿的新鲜组织及父母外周静脉血进行相关基因测序分析, 并通过Sanger测序进行家系分析及位点验证。结果胎儿组织样本检测到PKHD1基因存在c.5336A>T(p.Asn1779Ile)和c.9455delA(p.Asn3152Thrfs*10)复合杂合变异, Sanger测序结果显示父亲携带c.5336A>T(p.Asn1779Ile)杂合变异, 母亲携带c.9455delA(p.Asn3152Thrfs*10)杂合变异, 因此胎儿的变异分别来源于其父母。经检索相关数据库及文献均为未报道的新变异。结论 PKHD1基因的c.5336A>T和c.9455delA变异可能为该家系患儿的致病原因, 本研究结果为家系的遗传咨询和临床产前诊断提供了依据。     

常染色体显性遗传型多囊肾病的研究进展

常染色体显性遗传型多囊肾病（ADPKD）是一种常见的遗传性肾病,可累及多个系统,最终导致肾功能衰竭,严重危害着人类健康,也是国际肾脏病领域研究的热点之一。本文对近年来ADPKD在分子诊断、发病机制和治疗等方面的研究进行了系统综述。     

常染色体显性遗传性多囊肾病合并蛛网膜下腔出血一家系

先证者 ( 2 )　男 ,49岁。 1984年 7月因肝大做 B超诊断为多囊肾、多囊肝。 1985年 5月 9日因突然剧烈头痛住院 ,查体 :意识清 ,Bp 16 0 / 10 0 mm Hg(1mm Hg=0 .133k Pa) ,颈部抵抗 ( ) ,腰穿为血性脑脊液 ,诊断为蛛网膜下腔出血 (SAH)。6月 3日排便时突然呼吸心跳停止死亡。家系调查　本家系 4代人中有 9人患病 (图 1)。 7,男 ,35岁。因无痛性血尿先后做肾盂造影和 B超 ,诊断为多囊肾、多囊肝。1个月后突发剧烈头痛、呕吐住院 ,查体 :中度昏迷 ,Bp 170 /10 0 mm Hg,颈抵抗 ( ) ,腰穿 :血性脑脊液 ,诊断 SAH,治疗好转出院。 6,女性…     

常染色体隐性遗传视网膜色素变性的相关基因研究进展

视网膜色素变性 (retinitis pigmentosa,RP)是一组进行性的可致盲的单基因遗传性视网膜疾病 ,以视网膜光感受器和色素上皮功能进行性受损为主要特征。常染色体隐性视网膜色素变性 (autosom al recessive RP,ad RP)属视网膜色素变性的一种类型 ,具有遗传异质性和临床异质性。目前已克隆了 15个致病基因 ,包括 PDEA、PDEB、CNGA 1、ABCA4、RL BP1、RPE6 5、TU L P1和 CRB1等 ,现简介如下。     

Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD), characterized by progressive cystic degeneration of the kidneys and congenital hepatic fibrosis (CHF), is the most common childhood onset ciliopathy, with an estimated frequency of 1 in 20,000 births. It is caused by mutations in PKHD1. The carrier frequency for ARPKD in the general population is estimated at 1 in 70. Given the recessive inheritance pattern, individuals who are heterozygous for PKHD1 mutations are not expected to have clinical findings. We performed ultrasound (USG) evaluations on 110 parents from 64 independent ARPKD families and identified increased medullary echogenicity in 6 (5.5%) and multiple small liver cysts in 10 parents (9%). All ARPKD parents with these abnormal imaging findings were asymptomatic; kidney and liver function tests were unremarkable. Complete sequencing of PKHD1 in the 16 ARPKD parents with abnormal imaging confirmed the mutation transmitted to the proband, but did not reveal any other pathogenic variants. Our data suggest that carrier status for ARPKD is a predisposition to polycystic liver disease and renal involvement associated with increased medullary echogenicity on USG. Whether some of these individuals become symptomatic as they age remains to be determined.     

Autosomal recessive polycystic kidney disease

Summary Autosomal recessive polycystic kidney disease is a rare inherited disorder which usually becomes clinically manifest in early childhood, whereas autosomal dominant polycystic kidney disease usually is a disorder of adult onset. With increasing knowledge and improving diagnostic techniques, it becomes evident that the spectrum of both entities is much more variable than generally known. The presentation of autosomal recessive polycystic kidney disease at later ages and survival into adulthood have been reported. The diagnostic criteria, clinical course, genetics and differential diagnosis of autosomal recessive polycystic kidney disease will be presented.Abbreviations ADPKD, ARPKD autosomal dominant/recessive polycystic kidney disease - CHF congenital hepatic fibrosis     

Autosomal recessive polycystic kidney disease

 Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited disorder which usually becomes clinically manifest in early childhood, although the spectrum of ARPKD is much more variable than generally known. Presentation of ARPKD at later ages and survival into adulthood have been observed in many cases. The responsible gene has been mapped to chromosome 6p. Thus there is no evidence of genetic heterogeneity. The most important indication for DNA diagnosis is the prenatal diagnosis in families with at least one affected child. The critical region has been narrowed with the use of recombinant families of about 4 cM. Several possible candidate genes have been excluded. Received: 23 April 1997 / Accepted: 12 August 1997     

New options for prenatal diagnosis in autosomal recessive polycystic kidney disease by mutation analysis of the PKHD1 gene

Due to the poor prognosis of severe autosomal recessive polycystic kidney disease (ARPKD), there is a strong demand for prenatal diagnosis (PD). Reliable PD testing is possible by molecular genetic analysis only. Although haplotype-based analysis is feasible in most cases, it is associated with a risk of misdiagnosis in families without pathoanatomically proven diagnosis. Linkage analysis is impossible in families where DNA of the index patient is not available. Direct mutation analysis of the recently identified polycystic kidney and hepatic disease 1 gene opens new options in families to whom a reliable PD cannot be offered on the basis of linkage analysis. We for the first time report two cases with PD based on mutation detection, illustrating the new options for PD in ARPKD.     

Genetics and phenotypic characteristics of autosomal dominant polycystic kidney disease in Finns

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to renal insufficiency and renal transplantation. Mutation screening in the major gene for ADPKD, the polycystic kidney disease type 1 (PKD1) gene, has often been incomplete because of multiple homologous copies of this gene elsewhere on chromosome 16. Furthermore, there are only a few studies investigating genotype–phenotype correlations in patients with ADPKD. In this study, we screened the entire coding region of the PKD1 and PKD2 genes in 17 Finnish families with ADPKD via long-range polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing. We were able to identify mutations co-segregating with ADPKD in all 16 families linked to PKD1 by haplotype analysis. Of these mutations, six were insertions/deletions, five nonsense mutations, and five missense mutations. In the only PKD2-linked family, we found a missense mutation, R322Q. With the exception of one mutation (L845S in PKD1), all mutations were novel. Mutations and their location did not have a strong correlation with the phenotype with the exception of subarachnoidal hemorrhage or brain aneurysm, where mutations were located more often at the 5 end of the PKD1 gene than at the 3 end of the PKD1 gene.Electronic Supplementary Material Supplementary material is available for this article at .     

Mutational analysis of PKD1 gene in a Chinese family with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease and common renal disease. Mutations of PKD genes are responsible for this disease. We analyzed a large Chinese family with ADPKD using Sanger sequencing to identify the mutation responsible for this disease. The family comprised 27 individuals including 10 ADPKD patients. These ADPKD patients had severe renal disease and most of them died very young. We analyzed 6 survival patients gene and found they all had C10529T mutation in exon 35 of PKD1 gene. We did not found gene mutation in any unaffected relatives or 300 unrelated controls. These findings suggested that the C10529T mutation in PKD1 gene might be the pathogenic mutation responsible for the disease in this family.