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.

Objective To evaluate the clinical significance of bone marrow minimal residual disease (MRD) monitoring by multi-parameter flow cytometry (FCM) regularly after the first complete remission (CR1) in patients with acute myeloid leukemia (AML).Methods A total of 63 paitents with AML who had got CR1 after chemotherapy were regularly monitored for MRD in bone marrow by FCM,and MRD ≥ 10-4 was positive.According to the latest standards of National Comprehensive Cancer Network (NCCN) for disease risks,they were categorized into three groups:better risk group (20 cases),intermediate risk group (27 cases) and poor risk group (16 cases).The probability of continuous complete remission (CCR) was calculated by KaplanMeier formula,and the statistical difference between MRD positivc and MRD negative CCR probabilities was evaluated by log-rank test.Results The positive rates of MRD were 20％(4/20),30％(8/27) and 10/16 in better risk group,intermediate risk group and poor risk group respectively.The difference between better risk group and intermediate risk group had no statistical significance (P=0.454),and the difference between poor risk group and intermediate risk group had statistical significance (P =0.035).Twenty-two cases showed positive MRD,and 41 cases showed negative MRD.The probability of CCR at 24 and 36 months in MRD positive patients were 18％ (4/22),18％ (4/22),in MRD negative patients were 83％ (34/41),80％ (33/41),and there were significant differences (P ＜ 0.01).Conclusions The dynamic detection of MRD by FCM can be used to evaluate the therapeutic effect and prognosis of AML.MRD monitoring has important clinical significance and can help to adjust the intensity of chemotherapy,carry out individualized treatment,predict prognosis,and choose appropriate therapy.

Objective To analyze the mutations of causal genes in 5 children with primary distal renal tubular acidosis (dRTA),and explore their association of genotype and phenotype,so as to raise the awareness of the disease.Methods The whole exome sequencing was used to identify mutations in these 5 children from 5 families.Results A total of 4 different mutations of ATP6V0A4 gene were found in 2 dRTA children,including a novel heterozygous intron mutation (c.639 + 1G＞ A),a reported heterozygous nonsense variant (c.580C ＞T,p.Arg194*) and 2 novel heterozygous duplications (c.1504dupT,p.Tyr502Leufs*22;c.2351dupT,p.Phe785Ilefs*28).Two novel heterozygous missense mutations of ATP6V 1B 1 gene (c.409C ＞ T,p.Pro 137Ser;c.904C ＞ T,p.Arg302Trp) were identified in the third child,and a heterozygous missense mutation of SLC4A1 gene (c.1765C ＞ A,p.Arg589Ser) previously reported was found in the fourth child.No mutation of the dRTA-related causal genes was found in the fifth child.Furthermore,the mutations of causal genes in each of the first three children were compound heterozygous,which were consistent with the autosomal recessive inheritance pattern,and the variant from the fourth child was de novo.Conclusions The present study has found 7 mutations,including 5 novel variants,which enriches the human gene mutation database (HGMD) and contributes to a better understanding of the disease mechanisms.

Objective:To systematically review the association between P2Y12 genetic polymorphisms and the clinical safety of clopidogrel in the patients with cardiovascular and cerebrovascular diseases. Methods:Retrieved from MEDLINE,Embase,CNKI,Si-noMed and Wanfang Database (from January 1995 to December 2016),array researches about the association between P2Y12 genetic polymorphisms and the clinical safety of clopidogrel were collected including the studies of patients taking clopidogrel with cardiovascu-lar and cerebrovascular diseases and excluding animal experimental studies. The bias of recruited studies was assessed and meta-analy-sis was performed by RevMan 5.1 software. Results:Totally 10 array researches(3 in English and 7 in Chinese) were enrolled invol-ving 5 223 patients. There were no statistical differences between T allele gene carriers and CC genetype patients of C34T in the inci-dence of adverse cardiovascular events (RR=0.95,95% CI:0.82-1.09,P=0.46). The incidence of adverse cardiovascular events in T allele gene carriers of G52T was higher than that in GG genetype patients(RR=1.99,95% CI:1.63-2.44,P<0.000 01). The incidence of clopidogrel resistance in T allele gene carriers of C34T was higher than that in CC genetype patients(RR=2.02,95% CI:1.37-2.96,P=0.000 4). The incidence of clopidogrel resistance in T allele gene carriers of G52T was higher than that in GG gene-type patients (RR=1.56,95% CI:1.04-2.34,P=0.03). There was no statistical difference in the risk of clopidogrel resistance be-tween C allele gene carriers of i-T744c and T allele gene no-carriers(RR=0.99,95% CI:0.78-1.25,P=0.92). Conclusion:T al-lele gene carriers of C34T might be a risk factor of the occurrence of clopidogrel resistance,T allele gene carriers of G52T might be a risk factor of the occurrence of cardiovascular events and clopidogrel resistance,and C allele gene carriers of i-T744c might not increase the danger of the occurrence of clopidogrel resistance.

Objective To investigate the prevalence of human parvovirus B19(B19V)infection among college students,so as to provide reference for the development of blood donor screening strategies and blood supply policies.Meth-ods From March 2023 to February 2024,blood donor samples from college students in Changchun were retrospectively an-alyzed using the principle of random numbers,with samples taken 1 to 3 days per month.B19V IgG/IgM were detected by ELISA,and B19V DNA and viral load were measured by real-time quantitative PCR.Results Among 1 456 blood donor samples from college students,the positive rates for B19V IgG,IgM and DNA were 11.54%,0.34%and 2.68%,respec-tively.The viral load in 39 B19V DNA-positive samples ranged from 5.60×102 IU/mL to 9.10×106 IU/mL,with 28 samples(1.92%)having a viral load above 104 IU/mL.There were 11 samples(0.76%)that were positive for B19V DNA but neg-ative for IgG/IgM.Conclusion The college students have a low prevalence of past B19V infection,but a higher risk of in-fections and a higer proportion of acute infections with high viral loads in individuals who are]B19V IgG negative,presenting a risk of transmission through blood transfusion.Targeted blood safety monitoring is necessary for college students to track the prevalence of B19V DNA.

De novo variants (DNVs) are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Presently, a plethora of DNVs have been identified using next-generation sequencing, and many efforts have been made to understand their impact at the gene level. However, there has been little exploration of the effects at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues. Therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate a better usage and improve the isoform-level interpretation of variants, we developed NeuroPsychiatric Mutation Knowledge Base (PsyMuKB). It contains a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.

The gene mutations of a patient with fructose-1,6-bisphosphatase (FBPase) deficiency and her parents were analyzed and her clinical manifestations, laboratory tests, and genetic characteristics were reviewed. The molecular analysis of FBP1 gene showed a G residue duplication at base 960 in exon 7(c. 960dupG) in this patient while her parents carried the heterozygous c. 960dupG mutation. The prominent clinical feature of this patient was the benign course of the disease with age. However, acute attack could be triggered by stress, long-time fasting, a large amounts of fructose intake, etc. The typical clinical manifestations were severe lactic acidosis, hypoglycemia, and elevated liver enzymes.

Objective To analyze the mutations of SLC12A1 gene in nine Chinese families with Bartter syndrome type I (BS1),and analyze the relationship between genotype and phenotype.Methods The next generation sequencing was used to detect mutations in nine BS1 patients including eight with antenatal BS (aBS) and one with classical BS (cBS).Clinical characteristics and biochemical findings at the first admission as well as follow-up were reviewed.Results 15 different mutations of SLC12A1 gene were identified,including 11 novel ones.Among nine probands,seven were compound heterozygotes,two were homozygotes.All patients presented with polydipsia and polyuria,and eight with growth retardation.All patients had lower than-normal serum chloride concentration,metabolic alkalosis,and elevated basal renin activity and aldosterone,and seven had hypokalemia.Through treatment of indomethacin and/or potassium chloride,biochemical indicators could roughly restored normal.Conclusion These findings will enrich the human gene mutation database (HGMD) and provide valuable references to the genetic counseling and diagnosis for Chinese population.