BACKGROUND Gitelman syndrome(GS)is an unusual,autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.It is caused by mutations in the solute carri...BACKGROUND Gitelman syndrome(GS)is an unusual,autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.It is caused by mutations in the solute carrier family 12 member 3(SLC12A3)gene resulting in disordered function of the thiazidesensitive NaCl co-transporter.To date,many types of mutations in the SLC12A3 gene have been discovered that trigger different clinical manifestations.Therefore,gene sequencing should be considered before determining the course of treatment for GS patients.CASE SUMMARY A 55-year-old man was admitted to our department due to hand numbness and fatigue.Laboratory tests after admission showed hypokalemia,metabolic alkalosis and renal failure,all of which suggested a diagnosis of GS.Genome sequencing of DNA extracted from the patient’s peripheral blood showed a rare homozygous mutation in the SLC12A3 gene(NM_000339.2:chr16:56903671,Exon4,c.536T>A,p.Val179Asp).This study reports a rare homozygous mutation in SLC12A3 gene of a Chinese patient with GS.CONCLUSION Genetic studies may improve the diagnostic accuracy of Gitelman syndrome and improve genetic counseling for individuals and their families with these types of genetic disorders.展开更多
BACKGROUND To screen for possible pathogenic loci in a patient with Gitelman syndrome by high-throughput exome sequencing and to explore the relationship between genotype and phenotype. CASE SUMMARY The clinical data ...BACKGROUND To screen for possible pathogenic loci in a patient with Gitelman syndrome by high-throughput exome sequencing and to explore the relationship between genotype and phenotype. CASE SUMMARY The clinical data of the patient were collected. Peripheral blood samples were obtained to isolate white blood cells and extract genomic DNA. High-throughput whole exome sequencing for candidate pathogenic genes in the proband was completed by the Huada Gene Technology Co. Ltd (Shenzhen, China). Sequencing showed a novel heterozygous missense mutation (a G to A transition at nucleotide 2582) in exon 22 of the SLC12A3 gene, which resulted in a substitution of histidine for arginine at position 816 of the LRP1B protein and caused the occurrence of disease. CONCLUSION This is the first report of a new pathogenic mutation in SLC12A3. Further functional studies are particularly necessary to explore potential molecular mechanisms.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
Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a n...Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.展开更多
Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic...Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide- sensitive NaCl co- transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The childrenwere finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.展开更多
Background Gitelman syndrome(GS)is a rare autosomal recessive hereditary renal tubular disorder characterized by hypokalemia,metabolic alkalosis,hypomagnesemia,and hypocalciuria.Case presentation We report a rare case...Background Gitelman syndrome(GS)is a rare autosomal recessive hereditary renal tubular disorder characterized by hypokalemia,metabolic alkalosis,hypomagnesemia,and hypocalciuria.Case presentation We report a rare case of GS with homozygous loss of SLC12A3 presenting with epilepsy.The patient was a 21-year-old female who sought medical attention for seizures.Her condition primarily manifested as epilepsy,diarrhea,and weakness of limbs.Through genetic analysis,we confirmed the diagnosis of this case and formulated a comprehensive approach for its management.Conclusions This case report extends the clinical symptoms of GS and provides a complete family of GS as a reference for subsequent studies.展开更多
基金Supported by the National Natural Science Foundation of China,No.81700649.
文摘BACKGROUND Gitelman syndrome(GS)is an unusual,autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.It is caused by mutations in the solute carrier family 12 member 3(SLC12A3)gene resulting in disordered function of the thiazidesensitive NaCl co-transporter.To date,many types of mutations in the SLC12A3 gene have been discovered that trigger different clinical manifestations.Therefore,gene sequencing should be considered before determining the course of treatment for GS patients.CASE SUMMARY A 55-year-old man was admitted to our department due to hand numbness and fatigue.Laboratory tests after admission showed hypokalemia,metabolic alkalosis and renal failure,all of which suggested a diagnosis of GS.Genome sequencing of DNA extracted from the patient’s peripheral blood showed a rare homozygous mutation in the SLC12A3 gene(NM_000339.2:chr16:56903671,Exon4,c.536T>A,p.Val179Asp).This study reports a rare homozygous mutation in SLC12A3 gene of a Chinese patient with GS.CONCLUSION Genetic studies may improve the diagnostic accuracy of Gitelman syndrome and improve genetic counseling for individuals and their families with these types of genetic disorders.
文摘BACKGROUND To screen for possible pathogenic loci in a patient with Gitelman syndrome by high-throughput exome sequencing and to explore the relationship between genotype and phenotype. CASE SUMMARY The clinical data of the patient were collected. Peripheral blood samples were obtained to isolate white blood cells and extract genomic DNA. High-throughput whole exome sequencing for candidate pathogenic genes in the proband was completed by the Huada Gene Technology Co. Ltd (Shenzhen, China). Sequencing showed a novel heterozygous missense mutation (a G to A transition at nucleotide 2582) in exon 22 of the SLC12A3 gene, which resulted in a substitution of histidine for arginine at position 816 of the LRP1B protein and caused the occurrence of disease. CONCLUSION This is the first report of a new pathogenic mutation in SLC12A3. Further functional studies are particularly necessary to explore potential molecular mechanisms.
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.
文摘Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.
文摘Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide- sensitive NaCl co- transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The childrenwere finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.
文摘Background Gitelman syndrome(GS)is a rare autosomal recessive hereditary renal tubular disorder characterized by hypokalemia,metabolic alkalosis,hypomagnesemia,and hypocalciuria.Case presentation We report a rare case of GS with homozygous loss of SLC12A3 presenting with epilepsy.The patient was a 21-year-old female who sought medical attention for seizures.Her condition primarily manifested as epilepsy,diarrhea,and weakness of limbs.Through genetic analysis,we confirmed the diagnosis of this case and formulated a comprehensive approach for its management.Conclusions This case report extends the clinical symptoms of GS and provides a complete family of GS as a reference for subsequent studies.
