Two patients with coexistence of thyroid disease and suspected Gitelman's syndrome underwent SLC12A3 gene analysis. The results confirmed that both patients were compound heterozygotes of SLC12A3 gene mutation. Three novel variants of SLC12A3 were found in this study. This report suggests that Gitelman's syndrome may coexist with other disorders associated with hypokalemia, such as Graves' disease.

Objective To describe the clinical characteristics of one child with primary hyperoxaluria types Ⅲ, and to analyze the potential mutant genes in his family.Methods AGXT, GRHPR and HOGA1 genes were analyzed by direct sequencing analysis in this family.One hundred unrelated healthy subjects were also analyzed as controls.Results The child had early onset of symptoms (0.8 year).His principal clinical manifestation included nephrolithiasis and obstructive nephropathy, however his nephrocalcinosis was mild.And he presented high urine oxalate, high urine calcium, and lower citrate levels.Two novel heterozygous mutations in HOGA1 were identified (compound heterozygous), one mutation was a 2-bp substitution at the last position in exon 6 and the first position of intron 6 respectively (c.834_834 + 1GG ＞ TT);another was a guanine to adenine substitution of the last nucleotide of exon 6 (c.834G ＞ A).Both of these variants found in this study probably acted as splicing mutations.Direct sequencing analysis failed to find these mutations in 100 unrelated healthy subjects.In addition, a SNP (c.715G ＞ A, p.V239I) was found in this family.There were no mutations detected in AGXT and GRHPR.Conclusions Two novel mutations are identified probably in association with PH Ⅲ.This is the first description and investigation on mutant gene analysis of PHⅢ in Asia.

Objective To describe and analyze the clinical characters of patients with FRG from 7 Chinese families.Then analyze and identify their mutations in SGLT2 gene,and explore the association of genotype and phenotype.Methods Quantitative test for 24-hour urine glucose and other laboratory tests were carried out among 7 probands (14 patients in all) and their family members from 7 pedigrees (totaling 23 subjects).All coding regions,including intron-exon boundaries,were analyzed using PCR followed by direct sequence analysis.Results Five novel mutations in SLC5A2 gene were identified in this investigation,including four missense mutations (A Serine to Glycine at position 335 (c.1003A＞G,p.S335G),a Glutamine to Arginine at position 448 (c.1343A ＞ G,p.Q448R),an alanine to proline at position 474 (p.A474P,c.1420G ＞ C) and a glycine to aspartic acid at position 580 (c.1739G ＞ A,p.G580D) and a deletion in intron 7 (c.886(-10_-31)del).By the minigene studies using the pSPL3 plasmids,we confirmed the deletion c.886(-10_-31)del as a splicing mutation.In this study,the mutation c.886(-10_-31)del accounted for about 43％ of the total alleles (12/28).These patients with compound heterozygous or homozygous mutations manifested middle degree or severe glycosuria (Quantitative test for 24-hour urine glucose:10.56-50.68 g/1.73 m2),however those with heterozygous variants presented with mild to moderate glycosuria (Quantitative test for 24-hour urine glucose ≤ 2.45 g/1.73 m2).This fits co-dominant inheritance pattern.Conclusions Five novel mutations which may be related to FRG are found in this study,and c.886(-10-31) del may be a high frequency mutation in Chinese patients.

Objective To analyze and identify the mutations of ATP6V0A4 and ATP6V1B1 gene in autosomal recessive distal renal tubular acidosis (rdRTA) children,and study the association of genotype and phenotype. Methods Genome DNA was amplified by PCR.Mutations of ATP6V0A4 and ATP6V1B1 gene in 3 children from 3 families were examined by direct sequencing.One hundred unrelated healthy subjects were selected to evaluate all mutations found in this study. Results A novel homozygous nonsense mutation was identified in ATP6VOA4 gene in one child, and a novel heterozygous nonsense variant and a frame-shift alteration were found in another child.No mutation of both genes was found in the third child.Conclusions Study of mutant genes of rdRTA in Chinese patients is helpful to understand the association in genotype and phenotype and increase the level of cognition and treatment to this disease.

Objective To investigate the clinical features and the effect of gender differences on phenotype of Giteiman syndrome (GS) patients. Methods Clinical features and biochemical parameters were compared and analyzed to look for correlation between male and female GS patients. Results More male patients suffered from nocturia than female patients (P < 0.05), and there were no statistical differences in other clinical features between males and females. The level of serum creatinine was higher in male patients than that in female ones [(82.7±43.3) μmol/L vs (58.7±12.7) μmol/L], but estimated glomerular filtration rate was male patients and female patients. The urinary potassium and chloride excretion fraction were higher in male group than those in female group (33.0%±22.9% vs 17.0%±4.7%;2.30%±1.59% vs 1.23%±0.39%, P< 0.05, respectively). Statistical differences were not observed in other laberatory parameters. Three patients with impaired renal function were all male. Conclusions More male patients suffer from nocturia than female patients. Male patients seem to be prone to impaired renal function. It is speculated that different density of sodium-chloride cotransporter in renal tubule may account for gender differences.

Objective To analyze the mutations of causal genes in sixteen Chinese patients with suspicious Bartter syndrome,and follow up their treatment results.Methods Mutations were identified by the next generation sequencing and the multiplex ligation-dependent probe amplification (MLPA).Clinical and biochemical features at the first presentation as well as follow-up results were reviewed.Results 15 different CLCNKB gene mutations were identified in sixteen patients with BS,including 11 novel ones.A novel missense mutation and a novel small deletion were found from SLC12A1 gene.A novel gross deletion was found in CLCNKA gene.A recurrent missense mutation was identified from BSND gene.The whole gene deletion mutation of CLCNKB gene was the most frequent mutation (32％),and the rate of gross deletion was up to 50 percent in this group of Chinese patients.The most common clinical manifestations were development retardation (15/16),polydipsia and polyuria (15/16).All of the patients were detected with hypokalemia,hypochloremia and metabolic alkalosis.Indomethacin treatment had significant improvement to the stature and weight restoration.Conclusion The present study has found 19 mutations,including 14 novel ones,which enriches the human gene mutation database (HGMD) and provides valuable references to the genetic counseling and diagnosis of Chinese population.

Objective To analyze the characteristics of the genotype, phenotype, and follow-up of Gitelman's syndrome (GS) in the largest group of Chinese patients. Methods Sixty seven patients with GS underwent SLC12A3 gene analysis. Clinical characteristics and biochemical findings at the first presentation as well as follow-up were reviewed. Additionally, the associations of genotypes and phenotypes were explored. Results Forty-one different SLC12A3 mutations were identified in 67 patients with GS, including 11 novel ones, and 5 recurrent ones. 3 families (5. 7% ) had triple SLC12A3 mutations. Typical hypocalciuria and hypomagnesemia were not found in 6(9% ) and 8 (11. 9% )patients, respectively. In addition, male patients had an earlier age of onset and a higher urinary fraction excretion of electrolytes. 2 patients presented with chronic kidney disease, 13 (19. 4% ) with type 2 diabetes, 14 (20. 9% )with impaired glucose tolerance, and 5(7. 5% ) with impaired fasting glucose. Conclusion This study revealed 41 mutations in 67 Chinese patients with GS, including 11 novel variants and 5 high-frequency ones. Fraction excretion of electrolyte in urine may be more sensitive in the evaluation of phenotype compared with those of blood. It is difficult to correct hypokalemia and hypomagnesemia in GS. Patients with GS are at higher risk of the development of diabetes than ordinary people.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by the development of inflammation and fibrosis in the soft tissues of the retroperitoneum and other abdominal organs.RPF can be divided into two types:idiopathic and secondary.Some of the previously diagnosed idiopathic retroperitoneal fibrosis cases belong to the IgG4-related disease category.In order to help clinicians to achieve better diagnostic accuracy,the article reviews current national and international research on this disorder,and summarizes the epidemiological characteristics,the pathogenesis,the clinical manifestations,the microscopicand imaging features,and the most recent advances in the management of RPF.

Objective To describe the clinical characteristics,and to analyze the AGXT gene mutation in three siblings with primary hyperoxaluria type I (PHI).Methods AGXT gene mutation was analyzed by direct sequencing analysis in this family,and the minor allele status was also tested.One hundred unrelated healthy subjects were also analyzed as controls.Results Three mutations in AGXT were identified in each of three patients including two novel heterozygous missense mutations and one previously reported variant.One mutation was a methionine to leucine substitution at position 49 (p.M49L,c.145A ＞ C) in exon 1,one was an asparagine to isoleucine transition at codon 72 (p.N72I,c.215A ＞ T) in exon 2,and another was a heterozygous nonsense mutation at codon 333 (p.R333*).Both p.M49L and p.R333* occured in cis configuration with the minor allele IVS1 +74 bp.Conclusions Two novel mutations are identified probably in association with PHI,however their pathogenicity and potential molecular mechanisms should be explored by further investigations.This is the first investigation on mutant gene analysis of PHI in China.

Objective To explore the clinical characteristics of IgG4-related disease (IgG4-RD) in Chinese by detailed clinicopathological and laboratory assessments.Methods The baseline features of 36 patients with biopsy-proven disease were reviewed.The diagnosis was confirmed by pathology review according to consensus diagnostic criteria and clinicopathologic correlation.Disease activity and damage were assessed by the IgG4-RD responder index (RI).Results Thirty (83.3％) of the patients were male,while six were female,and the average age of onset was 65.1 years.All of the 36 patients had active disease,in which submandibular gland,lymph nodes,retroperitoneal tissue were the most common affected organs in this group of patients.Among 36 patients,77.7％ had elevated serum IgG4 concentrations and 44.4％ had hypocomplementemia.Patients with elevated serum IgG4 had a higher RI,a greater number of organs involved (P ＜ 0.01 for all comparisons).The correlation between serum IgG4 level and RI (r=0.737,P ＜ 0.01) was stronger than IgG,ESR,CRP and serum complement levels.The incidence of hypocomplementemia in IgG4-RD patients with renal involvement was higher than that in IgG4-RD patients with other organs involvement (P ＜ 0.01).Twenty-eight patients received glucocorticoids therapy,and had lower RI and serum IgG4 concentration after therapy (P ＜ 0.05).Conclusions Both IgG4-RD RI and IgG4 concentration may be regarded as assessment markers of disease activity and therapeutic effect of IgG4-RD.The diagnosis of IgG4-RD should be supported by histopathology and clinical features.