Identification of a fibrillin-1 gene mutation in a Chinese Marfan syndrome family

Background and Objective Marfan syndrome,a variable and heritable disorder of fibrous connective tissue,characterized by affecting skeletal,ocular and cardiovascular systems.With the research advancement of genetic mechanism,the diagnosis of Marfan syndrome,based on clinical manifestations and genetic evidence,is more accurate.The aim of this study is identification of genetic pathogenesis in a Chinese family.

A novel frameshift mutation in the beta-subunit of the epithelial sodium channel gene caused Liddle syndrome

Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.

A novel TGFBR2 gene mutation of type 2 Marfan syndrome in a Chinese family

Objective To report the clinical features and the screening Results of the pathogenic gene in type 2 Marfan syndrome patients,and the relationship between the transmembrane domain of TGFBR2 gene and the clinical phenotype.Methods The FBN1 and TGFBR2 genes were sequenced in the genomic DNA by Sanger sequence of type 2 Marfan syndrome pedigrees,and the protein structure prediction and genotype phenotypic analysis of the TGFBR2 gene transmembrane domain termination mutation were carried out.

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy

Background and Objective Desminopathy is a largely heterogeneous group of conditions involving inherited or sporadic myofibrillar myopathy.In terms of its mode of inheritance,the autosomal dominant form is predominant.Desmin gene(DES)mutations play a critical role among the pathogenic inherited factors associated with desminopathy.Desminopathy involves various phenotypes,mainly including different cardiomyopathies,skeletal myopathy and arrhythmia.The purposes of this study are characterization of a novel phenotype and identification of a DES splicing mutation in a Chinese family with desminnopathy.

Genotype-phenotype analysis of a novel mutation of FBN1 gene in a Chinese Marfan syndrome family

Objective causing mutation in a Marfan syndrome(MFS)family with a proband,and to establish genotype-phenotype correlations.Methods Genomic DNA from peripheral blood leukocytes of a Chinese Marfan syndrome familial were isolated and screened for fibrillin-1(FBN1)mutations by direct sequencing,and a genotypephenotype study was carried out following a review of the literature on mutations in the searched area.

Neurofibromatosis type Ⅰ caused by a splicing mutation in NF1 using targeted next generation sequencing

Objective Neurofibromatosis typeⅠ(NF1)is an autosomal dominant disorder which is caused by loss-of-function mutations in neurofibromin 1 gene(NF1).Clinically,NF1 mainly manifests several typical features,such as multiple neurofibromas and café-au-lait spots,as well as axillary freckling and Lisch nodules in iris.The aim of the current study is to identification a splicing mutation and genotype-phenotype correlation.

A novel heterozygous frameshift mutation in PKDl causing polycystic kidney disease

Objective Polycystic kidney disease(PKD),characterized by the presence of progressive fluid-filled cysts in renal mainly,is a lifethreatening genetic disorder which often develops into end-stage renal disease.Inherited pattern of PKD includes autosomal dominant and autosomal recessive.Autosomal dominant PKD is genetically heterozygous involving either of two genes,PKD1 or PKD2.The purpose of this study is to identify a novel frameshift mutation in PKD1 causing polycystic kidney disease.

一个Liddle综合征新SCNN1B基因移码突变的鉴定

Liddle综合征是一种由编码肾小管上皮细胞钠离子通道(ENa Cs)的SCNN1A、SCNN1B及SCNN1G基因突变引起的罕见单基因遗传性高血压,基于基因检测技术进行确诊并及时给予对应治疗可显著改善患者预后.由于发病率低,相关突变位点报道少,目前Liddle综合征突变位点谱仍不完善.本研究通过对野生型及突变型ENa Cs重组非洲爪蟾卵母细胞进行膜片钳检测,首次确定了SCNN1B基因中一个移码突变c.1691_1693delins G对Liddle综合征的致病性.进一步研究结果表明,突变型非洲爪蟾卵母细胞ENa Cs电流显著增加,这与已知的Liddle综合征发病机制一致.此外,本研究通过对该家系中接受阿米洛利/氢氯噻嗪复方制剂治疗的7名患者进行为期12个月的观察研究,发现所有患者血压控制理想,血清钾离子、血浆肾素及醛固酮水平正常,无心血管事件及严重药物不良反应发生.本研究有助于扩大Liddle综合征的基因诊断谱,并为该病的治疗方案提供参考.