Mutation spectrum and clinical features of congenital long QT syndrome in 20 children: a single center study / 中华实用儿科临床杂志

Objective:To explore the pathogenic genes, clinical characteristics and treatment follow-up of children with congenital long QT syndrome (LQTS).Methods:Clinical data of 20 cases diagnosed with congenital LQTS and underwent gene testing from April 15, 2011 to April 15, 2021 in Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University were retrospectively collected and analyzed using independent sample t-test and Fisher′ s exact probability method. Results:LQTS-related gene mutations were detected in all the 20 cases, and pathogenic or suspected pathogenic mutations were identified in 18 cases (90.0%). Five LQTS mutation genes were discovered, including KCNQ1, KCNH2, SCN5A, CACNA1C and AKAP9.Eighteen cases (90.0%) had positive symptoms, and 13 cases (65.0%) had definite inducements.The inducement of symptoms in children with LQTS type 1(LQT1) was related to exercise, the causes of syncope in LQT1 and Jervell-Lange-Nielsen syndrome type 1 (JLNS1) with complex heterozygous mutations were exercise or emotional agitation; the causes of syncope in LQTS type 2 (LQT2) were unrelated to exercise; severe exercise in LQTS type 3 (LQT3) resulted in symptoms; and seizure in LQTS type 8 (LQT8) was non-induced.The corrected QT(QTc) interval of 20 cases was (553.1±66.6) ms, with a range of 460-707 ms, among which 17 cases showed QTc≥480 ms.The electrocardiogram(ECG) manifestations of children with various types of LQTS were different.There was no significant difference in QTc between different genders, or between children with syncope and those without syncope (all P>0.05). The follow-up time was (3.4±2.3) years, ranging from 0 to 8.3 years.Seventeen children received treatment[beta blockers and implantable cardiovertor-defibrillator(ICD)] and 3 cases did not.By the end of the follow-up, 1 child died, 19 cases survived, and 2 cases of the surviving children lost consciousness. Conclusions:There is a high consistency between genetic diagnosis and clinical diagnosis of congenital LQTS.The positive rate of gene detection is 90.0%.The clinical manifestations and ECG characteristics vary with genotypes.Beta blockers are protective.ICD therapy can prevent sudden cardiac death when oral medication does not respond.

Detection of MSX1 gene mutations in patients with congenital tooth loss in Van der Woude syndrome / 口腔疾病防治

Objective@#To explore the relationship between MSX1 gene detection and tooth loss in a Van der Woude syndrome (VWS) family @* Methods @# DNA was extracted from the venous blood of 2 patients with dental hy⁃podontia in the 9th family of Van der Woude syndrome (VWS) families and 62 controls with complete dentition. Primers were designed for the MSXl gene. The coding regions of exons 1 and 2 of the MSX1 gene were amplified by PCR. The purified products of exons 1 and 2 of the MSX1 gene were sequenced and analyzed by sequence alignment @*Results@#The ivs2+68 C>T polymorphism in the MSX1 gene was found in the VWS9 members with tooth loss, and the VWS pa⁃tients with IRF6 gene mutations had increased tooth loss@* Conclusion@#Congenital tooth loss in the patients with con⁃genital missing teeth in VWS family 9 may be related to the ivs2 + 68 C> T polymorphism of the MSX1 gene.

Potent gene screening strategy based on family-based patients with lumbar discherniation / 西安交通大学学报(医学版)

Objective: To look for a potent gene that may cause intervertebral disc degeneration in a family with intervertebral disc herniation by exome sequencing four patients with intervertebral disc herniation so as to provide possible help for studies on the causes and mechanisms of intervertebral disc diseases. Methods: We collected the serum of patients with lumbar disc herniation treated at The First Affiliated Hospital of Xi'an Jiaotong University, The First Affiliated Hospital of Xi'an Medical College, and Xi'an Tangcheng Hospital from January 2010 to December 2016. A detailed medical history was collected and family survey was conducted to find a family with high incidence of degenerative intervertebral disc disease. Then we found 4 patients aged 20 to 50 years with lumbar disc herniation in this family. Exome sequencing was used to analyze the common exon mutation sites of the 4 patients to find the common mutation sites. Results: The common mutation IGFBP6, Chr12:g.53494591T>C, was detected in the 4 samples. The Sanger sequencing performed in-family validation revealed that the IGFBP6 showed a C/T type in all the four patients and a T type in all the five normal controls. Finally, verification was performed in 200 normal controls and no mutation was found in this site. Therefore, the IGFBP6 might be the effector gene that caused intervertebral disc degeneration in this family. Conclusion: The mutation site of IGFBP6, c.T430C (p.S144P) (Chr12:g.53494591T>C), may be a factor that contributes to the high incidence of intervertebral disc herniation in this family. We still need to verify the function of the gene in future. Our study has also confirmed that exome sequencing technology can be applied to the detection of disease-causing genes in complex diseases.

Progress of common gene mutations and detection methods of non-syndromic inherited hearing impair-ment / 国际儿科学杂志

Deafness is a seriously disabling disease affecting the quality of human life and genetic fac-tors account for a large proportion in the pathogenesis of newborn deafness.With the development of genomics technology,molecular genetics of hearing loss has become a cutting-edge field under investigation in otology. Molecular diagnostic technique plays an important role in exploring the pathogenesis,assisting clinical diagnosis and the prenatal diagnosis.In this review,we introduce the common pathogenic gene mutations and the diagnosis of non-syndromic inherited hearing impairment.

Antimicrobial susceptibility and pathogenic genes of Staphylococcus aureus isolated from the oral cavity of patients with periodontitis

PURPOSE: The goal of this study was to characterize the patterns of antimicrobial resistance and virulence genes in samples of Staphylococcus aureus (S. aureus) isolated from periodontitis patients. METHODS: From July 2015 to August 2015, oral saliva was collected from a total of 112 patients diagnosed with periodontitis, including 80 outpatients in dental hospitals and 32 patients in dental clinics located in Seoul and Cheonan. The samples were subjected to a susceptibility test to evaluate the prevalence of antimicrobial resistance, and the pathogenic factors and antimicrobial resistance factors in the DNA of S. aureus were analyzed using polymerase chain reaction. RESULTS: A susceptibility test against 15 antimicrobial agents showed that 88% of cultures were resistant to ampicillin, 88% to penicillin, and 2% to oxacillin. Resistance to at least two drugs was observed in 90% of cultures, and the most common pattern of multidrug resistance was to ampicillin and penicillin. Enterotoxins were detected in 65.9% of samples. The cell hemolysin gene hld was detected in 100% of cultures and hla was detected in 97.6% of samples. All strains resistant to penicillin and ampicillin had the blaZ gene. The aph(3')IIIa gene, which encodes an aminoglycoside modifying enzyme, was detected in 46.3% of samples. CONCLUSIONS: In the treatment of oral S. aureus infections, it is important to identify the pathogenic genes and the extent of antimicrobial resistance. Furthermore, it is necessary to study patterns of antimicrobial resistance and cross-infection in the context of periodontological specialties in which antimicrobials are frequently used, such as maxillofacial surgery, where the frequency of antimicrobial use for minor procedures such as implant placement is increasing.

Progress in the gene-related study on autosomal retinitis pigmentosa / 眼科研究

Retinitis pigmentosa (RP) is a common sight-threatening eye disease.RP is characterized by highly genetical and phenotypical heterogeneity.Identification of the causative genes of RP is the first step toward the understand of the molecular basis of RP and,subsequently,toward the prevention and treatment of RP.In recent years,there have been new progress in the study on RP.This review mainly focuses on recent advances in the gene-related studies of autosomal dominant RP (adRP) and autosomal recessive RP (arRP) with emphasis on the roles of common genes,as well as their possible mechanisms in RP in order to provide the essential reference for the genetics research of RP.