Objective： To determine the gene location of two Gitelman syndrome （GS） family SLC12A3 genes and explore treatments using Chinese medicine （CM） prescriptions. Methods： In order to locate the two GS mutations, sa...Objective： To determine the gene location of two Gitelman syndrome （GS） family SLC12A3 genes and explore treatments using Chinese medicine （CM） prescriptions. Methods： In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine （including potassium, Panangin and potassium-sparing diuretics） with CM prescription based on Buyang Huanwu Decoction （补阳还五汤） and Sijunzi Decoction （四君子汤）. The treatment included three stages, oral potassium chloride for the first 2 weeks （stage 1）, potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks （stage 2）, CM along with the medicine in stage 2 for the final 2 weeks （stage 3）. Results： The three mutations occurring in proband 1 from pedigree 1 were Thr60Met, 965-1_976de113ins12 （small indels mutation） and Ala122Ala （homozygous silent mutation）. Likewise, three mutations, Asn359Lys, Thr382Met and Arg913GIn, appeared in the proband 2 from pedigree Ⅱ. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L （baseline）, 2.5 mmol/L （stage 1）, 3.1 mmol/L （stage 2） and 3.9 mmol/L （stage 3） in the proband 1, and 2.8 mmol/L （baseline）, 3.1 mmol/L （stage 1）, 3.5 mmol/L （stage 2） and 4.3 mmol/L （stage 3） in the proband 2, respectively. The symptoms （numbness of limbs, weakness, palpitations, etc.） of both probands were all alleviated. Conclusions： The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS.展开更多
Objective: Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SN...Objective: Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in theSLC17A7 gene are associated with the treatment outcome of venlafaxine in a Chinese Han population with major depressive disorder.Methods: This prospective pharmacogenetic case-control study that involved genotyping of four SNPs ofSLC17A7 was conducted on 175 major depressive disorder patients of Chinese Han origin, aged 18 to 65 years, participated in the study from April 2005 to September 2006. Comparisons of allele and genotype frequencies of all SNPs were performed between the responder/remission group and the nonresponder/nonremission group. This study was approved by the Institutional Ethics Committee of Sichuan University (approval No. 20151112-265).Results: The allele and genotype frequencies of the four candidate SNPs inSCL17A7 showed no significant difference between responders and nonresponders. Meanwhile, no significant difference was detected in the four investigatedSLC17A7 SNPs between patients who did and did not exhibit remission. Although one of the investigatedSLC17A7 variants (rs1578944) demonstrated a significant association (P=0.022) with a response to venlafaxine after 6 weeks of treatment in the survival analysis, the association was unclear after a Bonferroni multiple comparisons test was conducted.Conclusion: No significant association exists between the four candidate SNPs (rs1043558, rs1320301, rs1578944, and rs74174284) inSLC17A7 and venlafaxine treatment in the Chinese Han population.展开更多
Hearing loss is the most frequent sensory disorder involving a multitude of factors, and at least 50% of cases are due to genetic etiology. To further characterize the molecular etiology of heating loss in the Chinese...Hearing loss is the most frequent sensory disorder involving a multitude of factors, and at least 50% of cases are due to genetic etiology. To further characterize the molecular etiology of heating loss in the Chinese population, we recruited a total of 135 unrelated patients with nonsyndromic sensorineural hearing loss （NSHL） for mutational screening of GJB2, GJB3, GJB6, SLC26A4, SLC26A5 IVS2-2A〉G and mitochondrial 12SrRNA, tRNASer（t/CN） by PCR amplification and direct DNA sequencing. The carrier frequencies of deafness-causing mutations in these patients were 35.55% in GJB2, 3.70% in GJB6, 15.56% in SLC26A4 and 8.14% in mitochondrial 12SrRNA, respectively. The results indicate the necessity of genetic screening for mutations of these causative genes in Chinese population with nonsyndromic heating loss.展开更多
BACKGROUND Gitelman syndrome(GS)is a rare inherited autosomal recessive tubulopathy,characterized clinically by hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis,and is caused by an inactivating mutatio...BACKGROUND Gitelman syndrome(GS)is a rare inherited autosomal recessive tubulopathy,characterized clinically by hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis,and is caused by an inactivating mutation in SLC12A3.GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism.It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia,which is difficult to correct.CASE SUMMARY A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo.However,the patient’s serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism.GS was confirmed by whole exome and Sanger sequencing.Gene sequencing revealed compound heterozygous mutations of c.488C>T(p.Thr163Met),c.2612G>A(p.Arg871His),and c.1171_1178dupGCCACCAT(p.Ile393fs)in SLC12A3.Protein molecular modeling was performed to predict the effects of the identified missense mutations.All three mutations cause changes in protein structure and may result in abnormal protein function.All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed.CONCLUSION We have identified a novel compound heterozygous mutation in SLC12A3.The present study provides new genetic evidence for GS.展开更多
基金Supported by grants from Fujian Province Natural Science Fund Project(No.2013J01277)Financial Scheme for Young Talents Training Programme of Fujian Health Industry(No.2013-ZQN-JC-6)
文摘Objective： To determine the gene location of two Gitelman syndrome （GS） family SLC12A3 genes and explore treatments using Chinese medicine （CM） prescriptions. Methods： In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine （including potassium, Panangin and potassium-sparing diuretics） with CM prescription based on Buyang Huanwu Decoction （补阳还五汤） and Sijunzi Decoction （四君子汤）. The treatment included three stages, oral potassium chloride for the first 2 weeks （stage 1）, potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks （stage 2）, CM along with the medicine in stage 2 for the final 2 weeks （stage 3）. Results： The three mutations occurring in proband 1 from pedigree 1 were Thr60Met, 965-1_976de113ins12 （small indels mutation） and Ala122Ala （homozygous silent mutation）. Likewise, three mutations, Asn359Lys, Thr382Met and Arg913GIn, appeared in the proband 2 from pedigree Ⅱ. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L （baseline）, 2.5 mmol/L （stage 1）, 3.1 mmol/L （stage 2） and 3.9 mmol/L （stage 3） in the proband 1, and 2.8 mmol/L （baseline）, 3.1 mmol/L （stage 1）, 3.5 mmol/L （stage 2） and 4.3 mmol/L （stage 3） in the proband 2, respectively. The symptoms （numbness of limbs, weakness, palpitations, etc.） of both probands were all alleviated. Conclusions： The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS.
基金This work was supported by the National Key Research and Development Program(Nos.2016YFC0906400,2016YFC1307000,2016YFC0905000,2017YFC0909200)the National Nature Science Foundation of China(Nos.81671326,81421061,81361120389,31701086)+4 种基金the Interdis-ciplinary Program of Shanghai Jiao Tong University(No.YG2019ZDA30)the Shanghai Key Laboratory of Psychotic Disorders(No.13dz2260500)Shanghai Municipal Science and Technology Major Project(No.2017SHZDZX01)the Shanghai Leading Academic Discipline Project(No.B205)the Capacity Building Planning Program for Shanghai Women and Children's Health Service(the Collaborative Innovation Center Project Construction for Shanghai Women and Children's Health,as well as the Project for Enhancing the Service Capacity of Shanghai Women and Children Health Care Institutions).
文摘Objective: Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in theSLC17A7 gene are associated with the treatment outcome of venlafaxine in a Chinese Han population with major depressive disorder.Methods: This prospective pharmacogenetic case-control study that involved genotyping of four SNPs ofSLC17A7 was conducted on 175 major depressive disorder patients of Chinese Han origin, aged 18 to 65 years, participated in the study from April 2005 to September 2006. Comparisons of allele and genotype frequencies of all SNPs were performed between the responder/remission group and the nonresponder/nonremission group. This study was approved by the Institutional Ethics Committee of Sichuan University (approval No. 20151112-265).Results: The allele and genotype frequencies of the four candidate SNPs inSCL17A7 showed no significant difference between responders and nonresponders. Meanwhile, no significant difference was detected in the four investigatedSLC17A7 SNPs between patients who did and did not exhibit remission. Although one of the investigatedSLC17A7 variants (rs1578944) demonstrated a significant association (P=0.022) with a response to venlafaxine after 6 weeks of treatment in the survival analysis, the association was unclear after a Bonferroni multiple comparisons test was conducted.Conclusion: No significant association exists between the four candidate SNPs (rs1043558, rs1320301, rs1578944, and rs74174284) inSLC17A7 and venlafaxine treatment in the Chinese Han population.
基金supported by the Research Grant Award from the National Natural Science Foundation of China (No.31171217)the Open Research Grant of Medical Key Department (No.XF200719) from Jiangsu Province (No.KF200910)Technology Developmental Program from Nanjing Medical University (No.09NJMUM005)
文摘Hearing loss is the most frequent sensory disorder involving a multitude of factors, and at least 50% of cases are due to genetic etiology. To further characterize the molecular etiology of heating loss in the Chinese population, we recruited a total of 135 unrelated patients with nonsyndromic sensorineural hearing loss （NSHL） for mutational screening of GJB2, GJB3, GJB6, SLC26A4, SLC26A5 IVS2-2A〉G and mitochondrial 12SrRNA, tRNASer（t/CN） by PCR amplification and direct DNA sequencing. The carrier frequencies of deafness-causing mutations in these patients were 35.55% in GJB2, 3.70% in GJB6, 15.56% in SLC26A4 and 8.14% in mitochondrial 12SrRNA, respectively. The results indicate the necessity of genetic screening for mutations of these causative genes in Chinese population with nonsyndromic heating loss.
基金Supported by the Science and Technology Plan of Health Commission of Jiangxi Province,No.202130648the Science and Technology Research Project of Department of Education of Jiangxi Province,No.GJJ201522.
文摘BACKGROUND Gitelman syndrome(GS)is a rare inherited autosomal recessive tubulopathy,characterized clinically by hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis,and is caused by an inactivating mutation in SLC12A3.GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism.It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia,which is difficult to correct.CASE SUMMARY A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo.However,the patient’s serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism.GS was confirmed by whole exome and Sanger sequencing.Gene sequencing revealed compound heterozygous mutations of c.488C>T(p.Thr163Met),c.2612G>A(p.Arg871His),and c.1171_1178dupGCCACCAT(p.Ile393fs)in SLC12A3.Protein molecular modeling was performed to predict the effects of the identified missense mutations.All three mutations cause changes in protein structure and may result in abnormal protein function.All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed.CONCLUSION We have identified a novel compound heterozygous mutation in SLC12A3.The present study provides new genetic evidence for GS.
