Interpretation of outpatient respiratory management of infants, children, and adolescents with post-prematurity respiratory disease: an official American Thoracic Society clinical practice guideline / 中华实用儿科临床杂志

In recent years, the management of respiratory diseases related to preterm birth has received extensive attention.In 2021, the American Thoracic Society brought together multidisciplinary experts in respiratory, neonato-logy, otolaryngology, sleep medicine, radiology and nursing specialties to develop Guidelines for outpatient respiratory management in infants, children, and adolescents with post-preterm respiratory disease (hereinafter referred to as the " Guideline" ), aiming to provide evidence-based medical evidence for standardized outpatient management of respiratory diseases associated with preterm birth at different ages.The Guideline was interpreted and summarized so that pediatric clinicians could correctly diagnose and treat these diseases, and understand and implement standardized outpatient management on the basis of evidence.

Screening and functional analysis of GATA-6 mutations in patients with nonsyndromic conotruncal defects / 中华实用儿科临床杂志

Objective@#To explore the molecular and genetic mechanism of transcription factor GATA-6 in nonsyndromic conotruncal defect (CTD) in order to provide evidence for early prevention and inheritance consultation of CTD.@*Methods@#A total of 32 cases of patients with nonsyndromic CTD and 100 healthy individuals were enrolled in the study.A total of 7 exons and bilateral partial intron-exon boundaries of GATA-6 were amplified by means of polymerase chain reaction (PCR). The PCR products were purified and directly sequenced by using an ABI Genetic Analyzer 3100 Automatic DNA sequence equipment.The acquired GATA-6 gene sequence was compared with standard gene sequence published in National Center for Biotechnology Information database, as well as the healthy control group to observe the GATA-6 gene mutations.The mutations were introduced into pcDNA3.1(+ ) by site-directed mutagenesis PCR on the basis of pcDNA3.1(+ )-GATA-6 in order to generate the GATA6-G245R mutant constructs.Wild type GATA-6, GATA-6-G245R and atrial natriuretic factor-luciferase(ANF-luciferase) were cotransfected into HEK 293T cells in vitro, and the CMV-LacZ were cotransfected as internal reference.Luciferase and galactosidase activity were measured by using luminometer 24 h after transfection and detected in the downstream ANF-luciferase reporter gene.@*Results@#A heterozygous missense mutation in the GATA-6 gene was identified in a patient with double outlets of the right ventricle.The mutation was located in Gly245Arg(G245R) in exon 2 of GATA-6.The mutation of pcDNA3.1(+ )-GATA-6 expression vectors were successfully constructed.Through the detection of luciferase reporter gene activity, it was found that GATA-6-G245R and wild-type GATA-6 decreased by 41.3%, and the comparison between them was statistically significant (P<0.001).@*Conclusions@#Transcription factor GATA-6 gene mutation is associated with the occurrence of nonsyndromic CTD.Transcription factor GATA-6 gene may be susceptible gene in human nonsyndromic CTD.

3M syndrome: a case report and literature review / 临床儿科杂志

Objective To investigate the clinical features and gene mutations of 3M syndrome. Method The clinical data of a child with 3M syndrome was retrospectively analyzed. The DNA was extracted from the peripheral blood of the child and parents, and the sequence analyses were performed by Agilent SureSelect exon capture and Illumina HiSeq sequencing platform. And the mutant gene was validated by Sanger sequencing. Results The six-month-old girl presented special face and growth retardation.The girl had a missense mutation c.4898C>T,p.T1633M in the CUL7 gene(NM_014780.4),and both her parents had heterozygous mutations.The girl was diagnosed with 3M syndrome.Conclusions The CUL7 mutation is the major causative gene of 3M syndrome in this girl. Early gene testing should be performed to confirm the diagnosis in suspected clinical phenotype.

Study of transcription factors GATA -4,-5,-6 of mutation screening in Chinese children with congenital heart disease / 中华实用儿科临床杂志

Objective To understand the relationship between GATA -4,-5,-6 gene mutations and con-genital heart disease(CHD),and to provide grounds for early prevention and genetic counseling of children with CHD. Methods GATA -4,-5,-6 coding regions exons and the flanking intron sequences in 1 98 CHD patients were screened,including 66 cases of the ventricular septal defects,84 cases of the atrial septal defects,and 48 cases of the nonsyndromic conotruncal heart defects patients.A total of 300 healthy subjects were selected as controls.The acquired sequences were aligned with which those publicized in GenBank by the aid of program BLAST.All exons and bilateral partial intron -exon boundaries of GATA -4,-5,-6 genes were amplified by the polymerase chain reaction (PCR). The PCR products were purified and directly sequenced by automatic DNA sequence equipment.The acquired GATA -4,-5,-6 gene sequences were compared with GenBank standard gene sequences with the aid of program BLAST. Results A heterozygous missense mutation in the GATA -4 gene was identified in a ventricular septal defect patient and a persistent truncus arteriosus patient.The mutation was located in c.799G >A(p.V267M)in exon 4 of GATA -4. Multiple aligenment of GATA -4 proteins across species demonstrated that altered amino acid was highly conserved. Transcription factor GATA -5,-6 screening showed no mutations in children with CHD in this study.Conclusions Transcription factor GATA -4 gene mutation may be associated with the occurrence of CHD.Transcription factor GATA -4 gene may be susceptible gene in human CHD.

Potential role of CRELD1 gene in the pathogenesis of atrioventricular septal defect / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen potential mutation of the CRELD1 gene in congenital atrioventricular septal defect (AVSD) and explore its functional implications.</p><p><b>METHODS</b>Fragments encompassing the 11 coding exons of CRELD1 gene, including at least 50 bp of flanking intronic regions, were amplified with PCR and subjected to DNA sequencing. Results of sequencing were compared with predicted sequence from the GenBank database. Eukaryotic expression vector pcDNA3.1CRELD1 containing the mutational sequence was constructed. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (FQ RT-PCR) was applied to examine the expression of CRELD1, Tenascin C and Aggrecan.</p><p><b>RESULTS</b>C857G was identified in a girl with an isolated partial AVSD. The mutation has resulted in a substitution of Alanine for Proline at amino acid 286 in the first cbEGF domain. Western blotting and FQ RT-PCR confirmed that the P286R missense mutation has been a gain-of-function mutation. Compared with the unloaded control, the Aggrecan mRNA expression was downregulated for both wild-type and mutant type samples (t=140.27 vs. 26.36, P < 0.01). The downregulation was more significant in mutant type (t=25.69, P=0.002). There was no significant difference of the Tenascin C expression between wild-type and the unload control (t=1.167, P> 0.05), whilst the Tenascin C expression was up-regulated in mutant type (t=6.66, P=0.022).</p><p><b>CONCLUSION</b>Mutation of the CRELD1 gene may increase the risk for AVSD rather than being directly causative. The P286R mutation of CRELD1 can downregulate the expression of Aggrecan and upregulates the expression of Tenascin C protein, both of which are crucial to extracellular matrix in the formation of the atrioventricular septum. The P286R mutation of CRELD1 may be correlated to the occurrence of AVSD.</p>

The role of transcription factor GATA-6 in heart development and congenital heart disease / 国际儿科学杂志

Congenital heart disease is caused by abnormal embryonic heart development.According to the research findings of developmental biology,different heart cells must be strictly regulated to ensure proper cell location and development.In the process of heart development,transcription factors play an important role in the regulation of gene expression.Zinc finger transcription factor GATA-6,an early indicator of myocardial cell development,is currently regarded as main candidate gene involved in the pathogenesis of congenital heart disease.GATA-6 gene mutations lead to changes in transcriptional activity of the gene product,which together with other relevant factors may play a role in the pathogenesis of congenital heart disease.

Clinical characteristics and therapeutic effect of tachycardia-induced cardiomyopathy in 22 children / 临床儿科杂志

Objectives To explore the clinical symptoms, therapy and prognosis of tachycardia-induced cardiomyopathy (TIC) in children. Methods Clinical data of 22 children with TIC from July 2007 to July 2012 were retrospectively analyzed. Results TIC was mostly seen in male infants and 81.82%of TIC was caused by atrial arrhythmias. The clinical symptom relieved after arrhythmia and ventricular rates were under control with average effective treatment time of (14.00 ± 8.20) days. Ten patients had tachycardia recurrence, 7 of them had atrial arrhythmia and their clinical symptoms were improved after treatment;while 3 of them showed longer time of therapy with average treatment time of (19.50±8.40) days (P<0.05). Five children underwent radiofrequency ablation before school age and got good therapeutic effect. The post-treatment echocardiographic parameters showed cardiac function of TIC children was significantly improved after treatment, including left ventricular end-diastolic diameter index, left ventricular end-systolic diameter index, left ventricular ejection fraction and shortening score (all P<0.05). Conclusions Childhood TIC is a reversible myocardial dysfunction and its prognosis is good. TIC can be induced by various types of tachyarrhythmias and normally by atrial arrhythmia. The preferred treatment of TIC is administration of antiarrhythmic drugs but radiofrequency ablation is needed to ventricular arrhythmias induced TIC.