Syndrome In Chinese Population Research Articles

Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature.

Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature. The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype-phenotype correlations. We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non-polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p < 0.001) and lower birth weight (33.3% vs. 3.2%, p = 0.030), with statistical significance. The patients with PARMs were more likely to have cardiovascular defects (64.9% vs. 27.3%, p = 0.063), cerebral hemorrhage (29.7% vs. 9.1%, p = 0.322) and seizures (37.8% vs. 9.1%, p = 0.151) than those with NPARMs, with no statistical significance. CCHS patients with PHOX2B NPARMs were more likely to have premature birth and low birth weight, while PHOX2B PARMs tended to be positively associated with the risk of cardiovascular defects, cerebral hemorrhage and seizures in Chinese population.

Identification of potential genetic Loci and polygenic risk model for Budd-Chiari syndrome in Chinese population

Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction, posing life-threatening risks in severe cases. Reported risk factors include inherited and acquired hypercoagulable states or other predisposing factors. However, many patients have no identifiable etiology, and causes of BCS differ between the West and East. This study recruited 500 BCS patients and 696 normal individuals for whole-exome sequencing and developed a polygenic risk scoring (PRS) model using PLINK, LASSOSUM, BLUP, and BayesA methods. Risk factors for venous thromboembolism and vascular malformations were also assessed for BCS risk prediction. Ultimately, we discovered potential BCS risk mutations, such as rs1042331, and the optimal BayesA-generated PRS model presented an AUC >0.9 in the external replication cohort. This model provides particular insights into genetic risk differences between China and the West and suggests shared genetic risks among BCS, venous thromboembolism, and vascular malformations, offering different perspectives on BCS pathogenesis.

The Progress of Colorectal Polyposis Syndrome in Chinese Population.

The pathogenesis, clinical phenotype, treatment strategy, and family management of hereditary tumor syndromes are different from those of sporadic tumors. Nearly a quarter of patients with colorectal cancer show significant familial aggregation and genetic predisposition, and 5 to 10% are associated with definite genetic factors. According to the clinical phenotype, it can be divided into nonpolyposis syndrome and polyposis syndrome. Among the polyposis syndrome patients with definite clinical symptoms, there are still some patients with unknown etiology (especially attenuated familial adenomatous polyposis), which is a difficult problem in clinical diagnosis and treatment. Therefore, for this rare disease, it is urgent to carry out multicenter studies, complete the gene variation spectrum, explore new pathogenic factors, and accumulate clinical experience. This article mainly introduces the research progress and related work of colorectal polyposis syndrome in China.

Family-based analysis of -675 4G/5G polymorphism in the PAI-1 gene of polycystic ovary syndrome in Chinese population

Previous studies have shown that 4G/5G polymorphism in promoter region of plasminogen activator inhibitor-1 (PAI-1) gene can affect insulin sensitivity by elevating the level and activity of plasma PAI-1. In order to elucidate the relationship between the polymorphism of PAI-1 gene and polycystic ovary syndrome (PCOS), we used transmission disequilibrium test (TDT) to study the family of PCOS. Eight hundred and fifty-five participants consisting of 285 trios (mother, father and offspring with PCOS) were recruited at the Center of Reproductive Medicine, Shandong University from July 2007 to August 2014. 4G/5G polymorphism of PAI-1 gene was genotyped using direct sequencing protocol and TDT was used to analyse the association between PAI-1 gene and PCOS. Though the 5G allele in PAI-1 gene was overtransmitted in families, no statistical significance existed and there was no association between PAI-1 gene and PCOS, indicating that PAI-1 gene was unlikely to play a major role in the aetiology of PCOS in Chinese population. Impact Statement What is already known on this subject? Some studies have shown that 4G/5G polymorphism in promoter region of plasminogen activator inhibitor-1 (PAI-1) gene can affect insulin sensitivity by elevating the level and activity of plasma PAI-1, participating in the formation of insulin resistance (IR). What do the results of this study add? Though the 5G allele in PAI-1 gene was overtransmitted in families, no statistical significance existed and there was no association between PAI-1 gene and polycystic ovary syndrome (PCOS). What are the implications of these findings for clinical practice and/or further research? PAI-1 gene was unlikely to play a major role in the aetiology of PCOS.

Association of BST1 polymorphism with idiopathic restless legs syndrome in Chinese population

Association of BST1 polymorphism with idiopathic restless legs syndrome in Chinese population

Association between egg consumption and metabolic syndrome in Chinese population: a cross-sectional study

ObjectivesMetabolic syndrome (MS) comprises a constellation of symptoms that include abdominal obesity, hypertension, hyperglycaemia and dyslipidaemia. Dietary intake is a crucial environmental risk factor for MS, but the exact association...

Comparison of the triglyceride glucose index and blood leukocyte indices as predictors of metabolic syndrome in healthy Chinese population

Triglyceride glucose (TyG) index and inflammatory markers are reported to have a positive association with metabolic syndrome (MetS). However, no previous study has assessed the value of TyG index and inflammatory markers as predictors of metabolic syndrome in the same study. This study looks at the comparison of the triglyceride index and blood leukocyte indices as predictors of metabolic syndrome in the Chinese population. The study cohort involved 1542 Chinese population without metabolic syndrome. The subjects underwent comprehensive routine health examination in 2011 and returned for a follow-up examination in 2016. Metabolic syndrome was defined according to Chinese Diabetes Society criteria, using body mass index for the replacement of waist circumference. TyG index, total leukocytes, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) were measured. Adjust d logistic models were used to assess the relationship between TyG index, blood leukocyte indices, and incident MetS. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of TyG index and blood leukocyte indices for MetS. Results from multivariate logistic regression analysis showed that, in the adjusted model, the subjects with the highest quartile of TyG index and neutrophils had a 3.894- and 1.663-fold increased incidence of MetS (P < 0.0001 and P = 0.027), respectively. No significant association was observed between total leukocytes, lymphocytes, NLR with incident MetS. ROC analysis showed that the AUC of TyG index and neutrophils were 0.674 and 0.568 for incident MetS, respectively. TyG index rather than blood leukocyte indices may have the strongest predictive value in MetS development over a 5-year period.

MALAT1 gene rs600231 polymorphism positively associated with acute coronary syndrome in Chinese population: a case-control study

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized as a major player in the pathogenesis of coronary artery disease (CAD). The aim of the study was to determine the association between polymorphisms of the MALAT1 gene and acute coronary syndrome (ACS) in a Chinese population in Xinjiang. In the case-control study, we genotyped three nucleotide polymorphisms (rs3200401, rs4102217, rs600231) of the MALAT1 gene using SNPscanTM typing assays (1,053 controls and 929 ACS patients). Furthermore, we explored a predictive model using MALAT1 rs600231 and clinical variables to predict the risk of ACS. Finally, the relative expression of long noncoding RNA (lncRNA) MALAT1 was also measured in 92 ACS patients and 92 controls using quantitative real-time polymerase chain reaction (qRT-PCR). The prevalence of the GG genotype of rs600231 in ACS group was higher than that in control group (15.7% vs. 14.7%, P=0.048). The dominant model differed (AG + GG vs. AA) and the G allele of rs600231 in ACS group was higher than that in control group (for dominant model: 66.2% vs. 60.9%, P=0.014; for allele: 41.0% vs. 37.8%, P=0.042). Multivariate logistic regression analysis and the predictive nomogram model showed that the dominant model of rs600231 remained an independent risk factor for ACS [odds ratio (OR) =1.32, 95% confidence interval (CI): 1.07-1.63, P=0.009]. The area under the receiver operating characteristic (ROC) curve (AUC) for the nomogram model for the prediction of ACS was 0.738 (95% CI: 0.716-0.761). In addition, in the AG and GG phenotypes, the relative expression of lncRNA MALAT1 was significantly higher in ACS patients than in controls with the same phenotypes (P<0.05). Among ACS group, compared to other genotype carriers, the relative expression level of MALAT1 in GG genotype carriers was higher (P<0.05). The present study suggested that the AG and GG genotype of rs600231 in MALAT1 gene was independently associated with ACS, and could be a risk genetic marker of ACS in a Chinese population in Xinjiang.

The prevalence and clinical characteristics of restless legs syndrome in patients with iron deficiency anemia in Korea.

While the prevalence and clinical characteristics of restless legs syndrome (RLS) are known to vary according to ethnicity, a detailed evaluation of this condition among patients with iron deficiency anemia (IDA) has not yet been reported in an Asian population. We investigated the prevalence and clinical characteristics of RLS in patients with IDA in Korea compared with age- and sex-matched patients diagnosed with idiopathic RLS. This prospective single-center study was performed at a regional university hospital. Consecutive patients with IDA were enrolled over a 4-year period. Clinical interviews and laboratory tests were conducted at the first visit. RLS diagnosis was confirmed through face-to-face interviews. We randomly selected patients with idiopathic RLS without comorbid medical disorders from our sleep center dataset as control patients. The clinical characteristics of both groups were compared. We enrolled 124 patients with IDA. Fifty (40.3%) patients were diagnosed with RLS, with 82% exhibiting severe to very severe symptoms. Patients with IDA and RLS were older and reported more sleep deterioration than patients with IDA without RLS. Patients with IDA and RLS also had a more depressed mood and higher periodic limb movement index scores than patients with idiopathic RLS. The prevalence of RLS among patients with IDA in Korea was high, with the majority having severe to very severe symptoms. Patients with IDA and RLS had poorer sleep quality and more emotional problems than patients with IDA without RLS. Therefore, patients with IDA should be screened for RLS to prevent adverse effects on the quality of sleep and life.

Interaction of General or Central Obesity and Hypertension on Diabetes: Sex-Specific Differences in a Rural Population in Northeast China.

PurposeSome studies have established an association between hypertension or obesity and the risk of diabetes. This study aimed to examine the interaction of hypertension and obesity on diabetes.Participants and MethodsThe data of 11,731 Chinese men and women were analyzed from the 2012–2013 Northeast China Rural Cardiovascular Health Study. The interaction was examined by both additive and multiplicative scales. General obesity was measured by body mass index (BMI); central obesity was defined by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR).ResultsAfter controlling for potential confounders, the odds ratios for diabetes were 3.864 (3.205–4.660), 4.500 (3.673–5.514), 4.932 (3.888–6.255) and 4.701 (3.817–5.788) for the combinations of hypertension and BMI, WC, WHtR or WHpR, respectively, which had the highest risk of diabetes among the four combinations. Notwithstanding the multiplicative interactions showed statistically significant in all analyses, the results of additive interactions were not consistent, suggesting the diabetes risk from female BMI (relative excess risk due to interaction (RERI): 1.136, 95% CI: 0.127–2.146, attributable proportion due to interaction (AP): 0.267, 95% CI: 0.057–0.477, synergy index (S):1.536, 95% CI: 1.017–2.321) or female WHpR (RERI: 1.076, 95% CI: 0.150–2.002, AP:0.205, 95% CI: 0.037–0.374, S:1.340, 95% CI: 1.012–1.775) was additive to the risk from hypertension.ConclusionThe findings suggest that high BMI and high WHpR have synergistic interactions with hypertension on the risk of diabetes for females. The results of this study also suggest that BMI and WHpR, rather than WC, should be used for the diagnosis of metabolic syndrome in Chinese population.

Association of BST1 polymorphism with idiopathic restless legs syndrome in Chinese population.

Parkinson's disease (PD) and restless legs syndrome/Willis-Ekbom disease (RLS/WED) are both common movement disorders. Based on their clinical overlap, association studies of PD and RLS/WED have been conducted for many years. To investigate whether or not the genetic risk factor of PD was also associated with RLS/WED. We included 102 idiopathic RLS/WED patients and 189 matched controls from southeast China. The clinical data included the International Restless Legs Syndrome Study Group Rating Scale, the subtypes of RLS/WED symptoms (painful or other discomfort), the comorbidities, the pregnancy history of female patients, the Hamilton Depression Scale (HAMD), and the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Risk gene analysis between RLS/WED and control groups including 21 SNPs (single nucleotide polymorphisms) was conducted. Genotyping was done by Sanger sequencing. We found that rs4273468 polymorphism of BST1 gene increased the risk of idiopathic RLS/WED patients in southeastern Chinese population (P = <0.001, OR = 2.85, p = 0.019 after Bonferroni correction). Moreover, the haplotype of G-G (rs4698412-rs4273468) was significantly associated with Chinese RLS/WED patients (p = <0.001). BST1 may contribute to the development of RLS/WED. Further studies on larger cohorts are needed to confirm these findings.

Rubinstein‐Taybi syndrome in Chinese population with four novel mutations

Rubinstein-Taybi syndrome (RSTS, OMIM*180849) is a rare autosomal dominant disorder, characterized by distinctive facial features, short stature, broad and often angulated thumbs and halluces, with occasional congenital anomalies. Characteristic facial dysmorphic features include downslanting palpebral fissures, low hanging columella. RSTS is caused by pathogenic variants in two ubiquitously expressed and highly homologous genes, CREBBP (OMIM*600140) and EP300 (OMIM*600140). Clinical features were well reported especially in Caucasian ethnicity. We would like to report the clinical phenotype of RSTS in our Chinese population and highlight four novel mutations in CREBBP gene.

Evaluation of small dense low-density lipoprotein concentration for predicting the risk of acute coronary syndrome in Chinese population.

BackgroundAcute coronary syndrome (ACS) is the leading cause of death in developing and developed countries, yet assessing the risk of its development remains challenging. Several lines of evidence indicate that small, dense low‐density lipoproteins (sd‐LDL) are associated with increased cardiovascular disease risk. We aim to evaluate sd‐LDL concentration for predicting the risk of ACS in Chinese population.MethodsBaseline characteristics of 121 patients with ACS and 172 healthy controls were obtained. Plasma sd‐LDL‐C was measured using homogeneous assay, and the proportion of sd‐LDL‐C in LDL‐C was detected.ResultsThere was gender and age effect on the sd‐LDL‐C concentration and sd‐LDL‐C/LDL‐C ratio among healthy subjects. Elevated sd‐LDL‐C concentrations and sd‐LDL‐C/LDL‐C ratio were observed in ACS patients with unstable angina pectoris (UAP), non–ST‐segment elevation myocardial infarction (STEMI), and ST‐segment elevation myocardial infarction (NSTEMI) compared with healthy controls (P < .05); however, there were no differences among ACS groups. According to Pearson's correlation coefficient analyses, sd‐LDL‐C concentration and sd‐LDL‐C/LDL‐C ratio were positively correlated with triglyceride (TG) and LDL‐C concentrations (P < .05) and negatively correlated with high‐density lipoprotein (HDL) concentration (P < .05). Based on the receiver operating characteristic (ROC) curves, the cutoff values of sd‐LDL‐C and sd‐LDL‐C/LDL‐C ratio for the prediction of ACS were 1.06 mmol/L and 34.55%, respectively. Multivariate logistic regression analysis demonstrated that the sd‐LDL‐C/LDL‐C ratio, but not sd‐LDL‐C concentration, was significantly associated with ACS events [OR (95% CI): 1.24, 1.11‐1.38, P < .001].ConclusionsThe sd‐LDL‐C/LDL‐C ratio may be associated with an increased risk of developing ACS in Chinese population.

A pan-cancer analysis of microsatellite instability as a predictor of Lynch syndrome in Chinese population.

1574 Background: Microsatellite instability (MSI) and mismatch repair deficiency (dMMR) are primarily tested in colorectal (CRC) and endometrial cancer (EC) to aid Lynch Syndrome (LS) diagnosis. A pan-cancer study presented at 2018 ASCO, however, revealed that up to 50% of LS patients had tumors not typically associated with LS, suggesting that patients with an MSI-high (MSI-H) phenotype should proceed to germline testing regardless of tumor type or family history. We thus set out to examine this potentially practice changing notion in Chinese population. Methods: MSI status and germline mutations in MLH1, MSH2, MSH6 and PMS2 genes were determined using a targeted next generation sequencing panel covering 100 MSI loci as well as MMR genes. Tumor mutation burden (TMB) levels were calculated for LS patients with MSI-H and MSS tumors, and intergroup differences were assessed using Mann Whitney U test or Fisher’s exact test. Results: Of 6,288 advanced tumors spanning &gt; 27 cancers, 0.8% (48/6,288) were EC, 21.6% (1,362/6,288) were CRC, and 77.6% (4,878/6,288) were other malignancies. 3.6% (224/6,288) of the samples were found to be MSI-H and 3.5% (217/6,288) harbored MMR mutations (somatic and germline). Germline mutations indicative of LS were identified in 0.1% (8/6,064) of the MSS group and 17% (38/224) of the MSI-H group (p &lt; 0.001). In contrast with the 2018 ASCO report, up to 63.8% of the 224 MSI-H tumors were CRC/EC, and only 8.9% (3/38) of the LS patients had MSI-H non-CRC/EC tumors (1 ovarian clear cell, 1 small bowel, and 1 gastric cancer). LS patients with non-CRC/EC tumors were more likely to be MSS compared to those with CRC/EC (70.0% vs 2.7%, p &lt; 0.001). Alterations in MLH1/ MSH2 were present in 78.3% (36/46) of the LS patients, and they demonstrated significantly better correlation with a MSI-H phenotype than MSH6/PMS2 alterations (94.4% vs. 40.0%, p = 0.0005). Additionally, in line with previous reports showing co-ocurrence of MSI-H and high TMB in gastrointestinal cancers, the LS patients with MSS tumors had a significantly lower median TMB compared with the MSI-H population (4.6 muts/Mb vs. 91.8 muts/Mb, p &lt; 0.001). Conclusions: Our study showed that in Chinese population, CRC/EC still predominated among LS-associated cancers, while non-CRC/EC LS patients were more likely to present with an MSS phenotype. The value of MSI-H/dMMR as a predictor of LS across different tumor types warrant further investigation.

Genetic Association Study of Restless Legs Syndrome in Chinese Population

Backgrounds: Several recent case-control studies have suggested some candidate genes being responsible for causing the restless legs syndrome (RLS). However, the association between those genes and the risk for RLS among the Asian population has not been well investigated. Objectives: The aim of the study was to investigate the genetic risk factors of RLS among the Chinese Population. Methods: A total of 158 RLS patients and 229 controls were recruited and the diagnosis of RLS was based on the criteria of International RLS Study Group. Polymer chain reaction and sequencing were used to detect 14 single nucleotide polymorphisms (SNPs) in 9 genetic loci (heme oxygenase 1 [HMOX1], HMOX2, vitamin D3 [1, 25-dihydroxyvitamin D3] receptor gene [VDR], interleukin 17A [IL17A], IL1B, NOS1, alcohol-dehydrogenase [ADH1B], gamma-aminobutyrate acid receptors[GABRR3] and GABRA4). Results: Among 14 selected SNPs, the frequency of IL1B rs1143634C allelic variant was lower in RLS patients than that in controls. Moreover, after adjustment for age and sex, rs731236 of VDR were found associated with increased risk of RLS in the dominant model. However, none of those results survived Bonferroni correction. The effects of HMOX1 and HMOX2 gene on developing RLS were not seen after the inclusion of RLS patients with a low ferritin level. Conclusions: Our study failed to replicate the association between 9 candidate genetic loci (HMOX1, HMOX2, VDR, IL17A, IL1B, NOS1, ADH1B, GABRR3 and GABRA4) and RLS in the Chinese population.

Clinical features and subtypes of restless legs syndrome in Chinese population: a study of 359 patients

BackgroundThe clinical spectrum of restless legs syndrome (RLS) has not been described in a Chinese population. We aim to evaluate the detailed clinical profile in a cohort of unselected RLS patients in China. MethodsWe enrolled RLS patients continuously according to the diagnostic criteria. Laboratory examinations were performed to exclude mimics and notable comorbidities. ResultsA total of 359 patients with RLS were enrolled. RLS symptoms were mostly symmetrical (65.2%), and purely unilateral RLS was not common (5.6%); however, unilateral dominant RLS was relatively more common. Only 1.1% of RLS patients reported no unpleasant sensations in the legs. The largest proportion of RLS patients described their uncomfortable sensation as indescribable (43.5%) and reported soreness (40.4%). In all, 8.9% of RLS patients described their abnormal sensation as painful, and 34.5% of RLS patients reported their symptoms fluctuated with seasonal trends. This population had a higher likelihood of an RLS family history. RLS patients with summer exacerbation had a younger age at RLS onset and longer disease duration (p < 0.01). Iron deficiency without anemia was common in Chinese RLS patients. Early-onset RLS patients were more likely to have a positive family history (p < 0.01), more summer worsening of symptoms (p < 0.01) and more severely disturbed peripheral iron status (p < 0.01) when compared to late-onset RLS patients. ConclusionThe subjective description is somewhat different, with Chinese RLS patients reporting less pain and more soreness than patients from Western countries. Seasonal fluctuation and iron deficiency without anemia are frequently seen in Chinese RLS patients and predict some other features. Differentiating these various subtypes can facilitate optimal management.

Association of HLA‐DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population

The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS. In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clinical features in primary nephrotic syndrome of children in Chinese population. Significant associations with PNS were found on missense SNP rs1129740 (GG vs AA, odds ratio (OR)=1.987, 95% confidence interval (CI)=1.468-2.652, P=0.00177049) and rs1047992 (AA vs GG, OR=1.857, 95% CI=1.325-2.391, P=1.1073E-10) of the HLA-DQA1 gene. This work suggests SNPs of HLA-DQA1 are risk factors for PNS in Chinese population, which implies roles of immune response in the pathogenesis of PNS.

Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome.

Background DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1,APEX1,MUTYH,OGG1,NUDT1,XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in Chinese population with Lynch syndrome.MethodsFrom Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DNA repair SNPs and CRC were calculated using a weighted Cox proportional hazard regression model.ResultsHeterozygous variants of rs1799832 in NUDT1 (HR = 2.97, 95% CI = 1.51–5.83) and rs13181 in ERCC2 (HR = 2.69, 95% CI = 1.10–6.55) were significantly associated with an increased risk of CRC compared with wild‐type homozygous CC and TT genotypes, respectively. However, the variant CG+GG genotype of MUTYH rs3219489 was associated with a decreased risk of CRC (HR = 0.49, 95% CI = 0.26–0.91) compared with the homozygous CC wild‐type counterparts.ConclusionOur findings revealed that polymorphisms of DNA repair genes that include NUDT1,ERCC2, and MUTYH are associated with CRC in patients with Lynch syndrome in Chinese population. Further studies with large sample size are needed to confirm our findings.

Clinical Characteristics of Wolfram Syndrome in Chinese Population and a Novel Frameshift Mutation in WFS1.

Wolfram syndrome (WS) is a rare, degenerative, and hereditary disorder characterized by ear diabetes mellitus (DM) and optic atrophy (OA). We aim to characterize clinical features in Chinese patients who had been poorly studied until now. We performed a retrospective review of patients with WS seen in the Peking Union Medical College Hospital from 2002 to 2017. Data including demographic data, clinical presentations, examination results, family history, and genetic analysis were described. Six patients with WS were identified, meeting the diagnostic criteria of the coincidence of DM and OA before 15 years old or the existence of two WFS1 mutations. All were male, with the median age of 14.5 years (range 10-19 years). Blood glucose impairment, OA, and diabetes insipidus were present in all (100%), hearing impairment in four (66.7%), urological abnormalities in four (66.7%), neurological abnormalities in one (16.7%), and endocrine disorder in one (16.7%). Rare presentation includes cataract, glaucoma, and spina bifida occulta. Diabetes was insulin-dependent and not ketosis onset, with antibody to glutamic acid decarboxylase and islet cell negative. Genetic analysis revealed mutations in WFS1 in three patients. A novel frameshift mutation (p.Asp151Glufs*93) was identified in exon 4 of WFS1. Our series of WS patients indicated that WS is a degenerative disease with a wide and variable spectrum, characterized by ear non-autoimmune DM and bilateral OA. Genetic analysis is recommended when suspected of WS.

Association of BTBD9 and MAP2K5/SKOR1 with restless legs syndrome in Chinese population

Study Objectives The aim of the study was to investigate the relationship between genetic factors and primary restless legs syndrome (RLS) in Chinese population. Methods A total of 116 RLS patients and 200 controls were recruited and the diagnosis of RLS was based on the criteria of International RLS Study Group. Polymer chain reaction (PCR) and sequencing were used to detect 19 single nucleotide polymorphisms (SNPs) in six genetic loci (MEIS1, BTBD9, PTPRD, MAP2K5/SKOR1, TOX3, and Intergenic region of 2p14). Results Our study found that one SNP increased the risk of RLS in Chinese population: rs6494696 of MAP2K5/SKOR1 (odds ratio [OR] = 0.09, p < .0001, recessive model). A further meta-analysis of RLS in Asian population found that two SNPs of BTBD9 increased the risk of RLS: rs9296249 of BTBD9 (OR = 1.44, p = .000, T allele), rs9357271 of BTBD9 (OR = 1.38, p = .021, dominant model). Conclusion Our results confirmed the association of BTBD9 and MAP2K5/SKOR1 with primary RLS in Chinese population.