Background: Gitelman's syndrome (GS) is an autosomal recessive renal tubular disorder, which is caused by the mutations in SLC12A3. This study was designed to analyze the characteristics of the genotype and phenotype, and follow-up in the largest group of Chinese patients with GS. Methods: Sixty-seven patients with GS underwent SLCl2A3 analysis, and their clinical characteristics and biochemical findings as well as follow-up were reviewed, aiming to achieve a better description of GS. Additionally, the association of genotype and phenotype was explored. Results: Forty-one different mutations were identified within these 67 GS patients, including 11 novel mutations and 5 recurrent ones. Typical hypocalciuria and hypomagnesemia were not found in 6 (9%) and 8 (11.9%) patients, respectively. Male patients and those harboring severe mutations in both alleles had significant higher urinary fractional excretion (FE) of potassium, magnesium and chlorine. In addition, there were 2 patients who had chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m²) and 32 patients with abnormal glucose metabolism. Conclusions: We identified 41 mutations related to GS, containing 11 novel variants and 5 high-frequency ones, which should facilitate earlier and more accurate diagnosis of GS. FE of electrolytes in urine may be more sensitive in the phenotype evaluation and differential diagnosis than corresponding serum electrolytes. Hypokalemia and hypomagnesemia in GS were difficult to correct; however, spironolactone might be helpful for hypokalemia to some degree. Compared with normal people, patients with GS were at higher risk of developing type 2 diabetes.

Familial renal glycosuria (FRG) is caused by mutations in the SLC5A2 gene, which codes for Na+-glucose co-transporters 2 (SGLT2). The aim of this study was to analyze and identify the mutations in 16 patients from 8 families with FRG. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Six mutations in SLC5A2 gene were identified, including five missense mutations (c.393G > C, p.K131N; c.1003A > G, p.S335G; c.1343A > G, p.Q448R; c.1420G > C, p.A474P; c.1739G > A, p.G580D) and a 22-bp deletion in intron 7 (c.886(-10_-31)del) removing the putative branch point sequence. By the minigene studies using the pSPL3 plasmids, we confirmed that the deletion c.886(-10_-31)del acts as a splicing mutation. Furthermore, we found that this deletion causes exclusion of exon 8 in the SCL5A2 transcript in patients. The mutation c.886(-10_-31)del was present in 5 (62.5%) of 8 families, and accounts for about 37.5% of the total alleles (6/16). In conclusion, six mutations resulting in FRG were found, and the c.886(-10_-31)del may be the high frequency mutation that can be screened in FRG patients with uniallelic or negative SLC5A2 mutations.

Pseudohypoaldosteronism type II ( PHAII ) is a rare renal tubular disease that is inherited in an autosomal dominant manner. Mutations in four genes ( WNK 1 , WNK 4 , CUL 3, and KLHL 3 ) have been identified to be responsible for this disease. Cullin 3 ( CUL 3) and KLHL 3 are subunits of Cullin– RING E3 ubiquitin ligase complexes, and the serine–threonine kinases WNK 1 and WNK 4 are substrates of this ubiquitin ligase. For CUL 3 , all mutations associated with PHAII exclusively lead to exon 9 skipping. In this study, we identified a Chinese PHAII kindred caused by a novel synonymous mutation (c.1221A > G p.Glu407Glu) in CUL 3 , and explored its effects on exon 9 abnormal splicing through an in vitro splicing assay and study of the patients’ RNA . We obtained evidence that this synonymous mutation leads to complete exon 9 skipping, and in silico bioinformatics analysis demonstrated that the CUL 3 c.1221A > G mutation might decrease the ratio of exonic splicing enhancers and silencers. This is the first report of PHAII in Chinese patients with a novel CUL 3 mutation. Our findings add a novel pathogenic splicing variant to the CUL 3 mutational spectrum and provide reference for further research on mechanisms of splicing modulation and development of potential therapeutic reagents for PHAII .

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive oxalate accumulation in plasma and urine, resulting in various phenotypes because of allelic and clinical heterogeneity. This study aimed to detect disease-associated genetic mutations in three PH1 patients in a Chinese family. All AGXT exons and 3 common polymorphisms which might synergistically interact with mutations, including P11L, I340 M and IVSI+74 bp were analyzed by direct sequencing in all family members. It demonstrated that in each of three patients, a previously reported nonsense mutation p.R333* was in cis with a novel missense mutation p.M49L in the minor allele characterized by the polymorphism of 74-bp duplication in intron 1, while the other novel missense mutation p.N72I was in trans with both p.R333* and P.M49L in the major allele. Kidney stones from two sibling patients were also observed though stereomicroscopic examination and scanning electron microscopy. Distinct morphological and inner-structure differences in calculi were noticed, suggesting clinical heterozygosity of PH1 to a certain extent. In brief, two novel missense mutations were identified probably in association with PH1, a finding which should provide an accurate tool for prenatal diagnosis, genetic counseling and screening for potential presymptomatic individuals.

Resources and the environment have always been the two important natural factors that affect people’s lives. In recent years, the problem of resources and the environment has increasingly become an important issue that people are concerned about. This study discusses the use and consumption of energy and the impact of environmental pollution on economic development under sustainable economic development. This paper takes Panzhihua as an example to analyze the impact of energy and environment on the economy, and proposes solutions to improve economic development, which is of strategic significance for the future development of Panzhihua City. In this paper, the system dynamics method is used to decompose the Panzhihua large-scale system into three parts and carry out modeling and simulation to explore the connection between them. Based on the data from 2007 to 2015 in Panzhihua City, simulations have been carried out to obtain qualitative and quantitative analysis of certain simulation curves of the energy-environment-economy 3E system (hereinafter referred to as 3E system) from 2007 to 2030 to ascertain the future development pattern of Panzhihua City. The results show that when the 3E system is a coordinated development model, economic development and environmental protection have a good development trend at the same time, which is applicable to the future development of Panzhihua City. This model has good reference suggestions and application prospects for urban development. We want to give Panzhihua City the following suggestions: (1) Continue to focus on the secondary industry and increase competitiveness. (2) Increase the investment funds in environmental protection and achieve sustainable economic development.