Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature

AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detecting the suspicious pathogenic variant type,the pathogenic variant sites of the patient and the patient’s family members were verified by multiple ligation dependent probe amplification and Sanger sequencing.Sift,polyphen-2,Mutation Taster and GERP++software were used to predict the pathogenicity of the unknown loci.The clinical data,diagnosis and treatment process of the patients were reviewed.Using the keyword“NF1;frameshift pathogenic variant”,relevant literature was gathered for analysis from Chinese and international databases,with articles dating from the establishment of each database to April 2022.RESULTS:A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient.The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497.Sanger sequencing validation and segregation analysis were performed,which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family.This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA(p.I1497Nfs*12).Relevant literature retrieval found 7 Chinese articles and 12 foreign articles.With NF1 gene mutation,mutation types are diverse,including point mutation,frameshift mutation,splice site mutation,exon mutation,chimeric mutation and de novo mutation.Foreign reports are based on autosomal dominant inheritance.CONCLUSION:This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family,expanding the mutational spectrum of the NF1 gene.

PREVALENCE AND RISK FACTORS OF PERIPHERAL ARTERIAL DISEASE IN DIABETIC PATIENTS OVER 50 YEARS OLD IN CHINA

Objective To investigate the prevalence of peripheral arterial disease (PAD) in China type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD. Methods In total 1 397 type 2 diabetic patients aged 50 years and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in 15 Class III Grade A hospitals in 7 major cities of China. Results Mean patient age was 63.7±8.2 years and mean duration of diabetes mellitus was 9.39±7.4 years. Two hundreds and seventy-two (19.47%) patients were diagnosed as PAD by ABI <0.9, 122 (18.37%) in male and 150 (20.46%) in female. PAD patients had a significantly longer duration of diabetes mellitus, higher hemoglobin Alc, and a significantly lower mean body mass index than non-PAD ones. Aging, smoking, and systolic blood pressure were found to be positively related with the prevalence of PAD. In terms of lipid profiles, no variable was found to relate with PAD. Notably, baPWV showed as the same significant guiding index for PAD, almost matched with ABI. Conclusions PAD is a common complication in China type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for diabetic patients with high risk factors.

A randomized, open-label, multicentre study to evaluate plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus and arteriosclerosis obliterans when treated with Probucol and Cilostazol

Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.

The current status of foot self-care knowledge, behaviours, and analysis of influencing factors in patients with type 2 diabetes mellitus in China

Purpose:To investigate the knowledge and behaviours on foot self-care in patients with type 2 diabetes mellitus;analyse the influential factors,and provide information for the intervention study.Methods:A total of 5961 patients with type 2 diabetes mellitus from 144 hospitals in China were included in the study.The investigation content included patients'demographic data,foot self-care knowledge and behaviours.The investigation tools were the questionnaires on the general diabetes information,on the foot self-care knowledge,and on the foot selfcare behaviours.Results:The foot self-care knowledge was medium and the foot self-care behaviour was poor.The status of knowledge and behaviours were influenced by education,duration of diabetes mellitus,periodic inspection,and education about diabetic complications.Pearson analysis demonstrated that there was positive correlation between knowledge score and behaviour score(r?0.27,p<0.001).Conclusions:The status of foot self-care knowledge and behaviours are not optimistic.According to the patients'own characteristics,the theory of knowledge,attitude and practice applies to encouraging patients to go for periodic inspection and education about diabetic complications so as to enhance the knowledge and promote the self-care behaviours.

Thyroid function of twin-pregnant women in early pregnancy

Background: Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies. Methods: Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018;160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies. Results: First-trimester reference ranges (4–12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01–3.35) mIU/L and FT4 16.38 (12.45–23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z =-1.964, P = 0.049);FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z =-6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z =-7.399, P = 0.000) in twin pregnancies in the first trimester. Conclusions: Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.

Evaluation of Diagnostic Efficiency of Ultrasound Features on Malignant Thyroid Nodules in Chinese Patients

Background： The aim of this study was to evaluate the efficacy of ultrasonic features in predicting the malignancy of thyroid nodules in a group of Chinese patients. Methods： In all, 762 patients with thyroid nodules （424 malignant and 338 benign） underwent ultrasound （US） check and surgery between March 2011 and July 2014 at Peking University First Hospital were identified. Univariate and receiver operating characteristic （ROC） analyses were performed to calculate the sensitivity, specificity, negative and positive predictive values of each US feature, and the accuracy of their combinations lbr prediction of malignancy. Results： Patients with malignant nodules were younger and without obvious risk history than those in the benign group （P 〈 0.001, P = 0.93 ）. No individual US sign was fully predictive of a malignant lesion. The Youden indexes of irregular margins and hypoechogenicity were the first and second highest in all US features, which were 51.9% and 45.2%, respectively. The sensitivity of solid components （89.7%） and hypoechogenicity （89.2%） and the specificity of taller-than-wide shape （98.5%） and microcalcifications （90.6%） were the first and second highest in all US features. Intranodular flow on a color Doppler examination was a weak predictor of malignancy. Under ROC analysis excepting intranodular flow, the 95% confidence interval （C1） of areas under tile curves of hypoechogenicity and irregular margins with any one of the US features were overlapped that of five-feature combinations （95% CI： 0.850 0.901）. Conclusions： We should be alert with taller-than-wide shape and microcalcifications, lntranodular flow was a weak predictor of malignancy. According to Youden indexes and ROC analysis, irregular margins and hypoechogenicity combined with solid component or taller-than-wide shapes or microcalcifications have a high predicative value for malignant thyroid nodules in Chinese patients.

Reversible renal infarctions associated with pheochromocytoma:a case report

To the Editor:The complications of pheochromocytoma caused by barely controlled hypertension and the overproduction of catecholamine can reduce patients’life expectancy and quality of life.Herein,we report a case of bilateral multiple renal infarctions on computed tomography(CT)scan related to pheochromocytoma,which achieved complete relief on follow-up after tumor removal.A 47-year-old male with a 3-year history of uncontrolled hypertension(the highest value recorded was 210/160 mmHg)and intermittent severe headache,pallor,and sweating presented to our hospital on April 15,2014.He did not monitor his blood pressure regularly but occasionally took dihydropyridine calcium-channel blockers.