Phenotypes and ATP7B gene variants in 316 children with Wilson disease / 中华儿科杂志

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.

Identification of a novel pathogenic mutation in PDHA1 gene for pyruvate dehydrogenase complex deficiency / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the molecular genetic mechanism and genetic diagnosis of pyruvate dehydrogenase complex deficiency (PHD), and to provide a basis for genetic counseling and prenatal genetic diagnosis of PHD.</p><p><b>METHODS</b>Polymerase chain reaction (PCR) was performed to amplify the 11 exons and exon junction of the PDHA1 gene from a child who was diagnosed with PHD based on clinical characteristics and laboratory examination results. The PCR products were sequenced to determine the mutation. An analysis of amino acid conservation and prediction of protein secondary and tertiary structure were performed using bioinformatic approaches to identify the pathogenicity of the novel mutation.</p><p><b>RESULTS</b>One novel duplication mutation, c.1111_1158dup48bp, was found in the exon 11 of the PDHA1 gene of the patient. No c.1111_1158dup48bp mutation was detected in the sequencing results from 50 normal controls. The results of protein secondary and tertiary structure prediction showed that the novel mutation c.1111 _1158dup48bp led to the duplication of 16 amino acids residues, serine371 to phenylalanine386, which induced a substantial change in protein secondary and tertiary structure. The conformational change was not detected in the normal controls.</p><p><b>CONCLUSIONS</b>The novel duplication mutation c.1111_1158dup48bp in the PDHA1 gene is not due to gene polymorphisms but a possible novel pathogenic mutation for PHD.</p>

Comparison of laxative and antioxidant activities of raw, processed and fermented Polygoni Multiflori radix / 中国天然药物

AIM@#To observe the anti-oxidative activity and adverse laxative effect of raw, traditional processed and fermented products of Polygoni Multiflori Radix (PMR), and furthermore, to evaluate the fermentation method used in the processing procedure of PMR.@*METHODS@#In vitro ferric reducing antioxidant power (FRAP) assay was carried out to evaluate the anti-oxidative activity. Modulation of normal defecation and effect on gastrointestinal motility in mice were carried out to investigate their adverse laxative effect.@*RESULTS@#Fermented PMR induced less severe laxative adverse effect than Polygoni Multiflori Radix Praeparata (PMRP). PMR fermented with Rhizopus sp. (FB) could modulate the defecation significantly. The gastrointestinal motility was inhibited by PMRP and PMR fermented with Rhizopus oryzae (FA). FA and FB showed better antioxidant activity than PMRP in 50% and 95% ethanol group. Contents of 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) were reduced significantly after traditional processing but maintained after fermentation. Emodin and physcion were increased after traditional processing and fermented with Rhizopus oryzae.@*CONCLUSION@#All processing procedure, including fermentation, might reduce its anti-oxidative activity. However, most of the processed products could lessen the adverse effect on gastrointestinal tract compared to PMR. Fermentation with Rhizopus oryzae was considered as a promising processing method of PMR.

Clinical and gene mutation analyses of three patients with ornithine carbamoyltransferase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical and genetic characteristics of three children with ornithine carbamoyltransferase deficiency(OTCD), and to provide a practical method for gene diagnosis and genetic counseling of the disease.</p><p><b>METHODS</b>All exons of the ornithine carbamoyltransferase (OTC) gene were screened by polymerase chain reaction-DNA direct sequencing in the three OTCD patients.</p><p><b>RESULTS</b>One patient firstly presented as vomiting at 6 month of age. A missense mutation of T262I was detected. His mother had the same mutation without any clinical symptoms. The second patient presented as restlessness, and had a missense mutation of R277W. Gene analysis of his parents was not available. The third patient presented as neonatal lethargy, harbored a missense mutation of I172M. His mother had the same mutation without any clinical symptoms.</p><p><b>CONCLUSION</b>Gene mutation analysis is a feasible way for diagnosing OTCD. Patients with I172M mutation present symptom early, while those with T262I and R277W mutations manifest symptoms later. Gene mutation analysis will be important for asymptomatic and prenatal diagnosis and genetic counseling.</p>

Adenovirus infection in hospitalized children with pneumonia in Guangzhou from 2005 to 2007 / 南方医科大学学报

<p><b>OBJECTIVE</b>To understand the characteristics of adenovirus infection in hospitalized children with pneumonia in Guangzhou area.</p><p><b>METHODS</b>The infection rate, hospitalization time and hospitalization expenses of adenovirus-infected hospitalized children with pneumonia in Guangzhou area from 2005 to 2007 were analyzed.</p><p><b>RESULTS</b>The total adenovirus infection rate was 6.04% in these children, with a male to female ratio of 1.47:1, showing significantly higher infection rate in female (7.92%) than in male patients (5.21%, P<0.05). The hospital stay and hospitalization costs between male and female children showed no significant difference (P>0.05). Adenovirus-infected children from birth to six years old accounted for 90.50% of the total adenovirus-infected children, and the infection rate in 0 to 1-year-old children (3.71%) was significantly lower than that in elder children (P<0.05). Although the infection rate in winter (8.44%) was significantly higher than that in the other seasons (P<0.05), the cases from March to August accounted for 60.11% of the total infected cases. Furthermore, the infection rate in 2007 (4.31%) was significantly lower than that in 2005 and 2006 (7.11% and 6.71%, respectively, P<0.05).</p><p><b>CONCLUSION</b>Adenovirus infection is an important pathogen in hospitalized children with pneumonia in Guangzhou area, and the infection rates differed between gender, age, season and the years.</p>

Rearrangement of immunoglobulin heavy chain variable region genes in human neonates / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the rearrangement of immunoglobulin (Ig) heavy chain variable region (V(H)) genes in human neonates with different gestational ages (GA).</p><p><b>METHODS</b>Peripheral blood from the neonates with GA of 27 weeks (4 cases), 28-32 weeks (9 cases), 33-36 weeks (12 cases), and 37-42 weeks (13 cases) was collected. RT-PCR was used to amplify the Ig V(H) gene, and the PCR products were separated by electrophoresis and analyzed using 6% denaturing PAGE gel.</p><p><b>RESULTS</b>All Ig V(H) family genes had several rearranged genes in each GA group, and the neonates with different GA showed no significant difference in the median molecular weight for each rearranged Ig V(H) family gene.</p><p><b>CONCLUSION</b>The neonates with GA of 27-42 weeks exhibit diversity in Ig V(H) gene rearrangement, and for the same Ig V(H) family, the median length of the arranged Ig V(H) genes is independent of the gestational age.</p>

Analysis of Respiratory Syncytial Virus Infection in Hospitalized Children with Pneumonia in Guangzhou Area from 2005 to 2007 / 实用儿科临床杂志

6-11 years old were 9.67%, 6.81%, 3.49% and 0.80%, respectively.Furthermore, the infection rates between each two age stages were significantly different(Pa0.05).4.Infection rates in 2005,2006 and 2007 were 4.0%, 8.92%, 8.85%,respectively.Infection rates between 2005 and 2006,2007 were significantly different(Pa