Background:Lowe syndrome,an X-linked,inheritable disease with clinical symptoms of congenital cataracts,incomplete Fanconi syndrome,and mental retardation,has an approximate incidence of 1 in 500000.Nearly 200 OCRL mu...Background:Lowe syndrome,an X-linked,inheritable disease with clinical symptoms of congenital cataracts,incomplete Fanconi syndrome,and mental retardation,has an approximate incidence of 1 in 500000.Nearly 200 OCRL mutations related to Lowe syndrome have been found worldwide,with only ten mutations among the Chinese population.Since more mutations may exist in Chinese patients,we sequenced and analyzed the OCRL genes of six children with Lowe syndrome in a medical center in China.Methods:Peripheral blood was collected from six children with Lowe syndrome and their relatives,and ten healthy adults.Genomic DNA was extracted from the blood and applied to amplify the twenty-four exons and flanking introns of the OCRL gene.The mutations were identified by sequencing.Results:Five mutations(c.1528C>T,c.2187insG,c.1366C>T,c.1499G>A,and c.2581G>A)of the OCRL gene were found in five families;c.2187insG and c.1366C>T were novel mutations.None of the five mutations were detected in 20 normal chromosomes.No mutation was found in the sixth family.Conclusion:Two novel mutations of the OCRL gene,c.2187insG and c.1366C>T,were found in Chinese patients with Lowe syndrome,which will provide new clues for the etiology of Lowe syndrome and could be beneficial to genetic diagnosis of the condition.展开更多
Background Dent disease is a rare tubulopathy characterized by manifestations of proximal tubular dysfunction,which occurs almost exclusively in males.It mainly presents symptoms in early childhood and may progress to...Background Dent disease is a rare tubulopathy characterized by manifestations of proximal tubular dysfunction,which occurs almost exclusively in males.It mainly presents symptoms in early childhood and may progress to end-stage renal failure between the 3rd and 5th decades of human life.According to its various genetic basis and to clinical signs and symp-toms,researchers define two forms of Dent disease(Dent diseases 1 and 2)and suggest that these forms are produced by mutations in the CLCN5 and OCRL genes,respectively.Dent diseases 1 and 2 account for 60% and 15% of all Dent disease cases,and their genetic cause is generally understood.However,the genetic cause of the remaining 25% of Dent disease cases remains unidentified.Data sources All relevant peer-reviewed original articles published thus far have been screened out from PubMed and have been referenced.Results Genetic testing has been used greatly to identify mutation types of CLCN5 and OCRL gene,and next-generation sequencing also has been used to identify an increasing number of unknown genotypes.Gene therapy may bring new hope to the treatment of Dent disease.The abuse of hormones and immunosuppressive agents for the treatment of Dent disease should be avoided to prevent unnecessary harm to children.Conclusions The current research progress in classification,genetic heterogeneity,diagnosis,and treatment of Dent disease reviewed in this paper enables doctors and researchers to better understand Dent disease and provides a basis for improved prevention and treatment.展开更多
基金supported by grants from the Science and Technology Program of Guangzhou(201300000168)Guangdong Provincial Population and Family Planning Projects(2012263)
文摘Background:Lowe syndrome,an X-linked,inheritable disease with clinical symptoms of congenital cataracts,incomplete Fanconi syndrome,and mental retardation,has an approximate incidence of 1 in 500000.Nearly 200 OCRL mutations related to Lowe syndrome have been found worldwide,with only ten mutations among the Chinese population.Since more mutations may exist in Chinese patients,we sequenced and analyzed the OCRL genes of six children with Lowe syndrome in a medical center in China.Methods:Peripheral blood was collected from six children with Lowe syndrome and their relatives,and ten healthy adults.Genomic DNA was extracted from the blood and applied to amplify the twenty-four exons and flanking introns of the OCRL gene.The mutations were identified by sequencing.Results:Five mutations(c.1528C>T,c.2187insG,c.1366C>T,c.1499G>A,and c.2581G>A)of the OCRL gene were found in five families;c.2187insG and c.1366C>T were novel mutations.None of the five mutations were detected in 20 normal chromosomes.No mutation was found in the sixth family.Conclusion:Two novel mutations of the OCRL gene,c.2187insG and c.1366C>T,were found in Chinese patients with Lowe syndrome,which will provide new clues for the etiology of Lowe syndrome and could be beneficial to genetic diagnosis of the condition.
基金supported by National Natural Foundation of China(81470939&81770710)Natural Science Foundation of Zhejiang Province(LH14H050002,LY15H050001,LQ18H050001)Ai You Foundation.
文摘Background Dent disease is a rare tubulopathy characterized by manifestations of proximal tubular dysfunction,which occurs almost exclusively in males.It mainly presents symptoms in early childhood and may progress to end-stage renal failure between the 3rd and 5th decades of human life.According to its various genetic basis and to clinical signs and symp-toms,researchers define two forms of Dent disease(Dent diseases 1 and 2)and suggest that these forms are produced by mutations in the CLCN5 and OCRL genes,respectively.Dent diseases 1 and 2 account for 60% and 15% of all Dent disease cases,and their genetic cause is generally understood.However,the genetic cause of the remaining 25% of Dent disease cases remains unidentified.Data sources All relevant peer-reviewed original articles published thus far have been screened out from PubMed and have been referenced.Results Genetic testing has been used greatly to identify mutation types of CLCN5 and OCRL gene,and next-generation sequencing also has been used to identify an increasing number of unknown genotypes.Gene therapy may bring new hope to the treatment of Dent disease.The abuse of hormones and immunosuppressive agents for the treatment of Dent disease should be avoided to prevent unnecessary harm to children.Conclusions The current research progress in classification,genetic heterogeneity,diagnosis,and treatment of Dent disease reviewed in this paper enables doctors and researchers to better understand Dent disease and provides a basis for improved prevention and treatment.
