多重连接依赖的探针扩增技术检测先天性心脏病患儿的22q11微缺失

目的 检测先天性心脏病患儿的22q11微缺失情况.方法 采用商品化的多重连接依赖探针扩增(Multiplex ligation dependent probe amplification,MLPA)P250试剂盒,检测100例散发的先天性心脏畸形样本,其中40例产前超声诊断为心脏畸形的胎儿,60例为先天性心脏病患儿.结果 心脏畸形的胎儿有2例为22q11微缺失,先天性心脏病患儿有1例22q11微缺失;3例检测出22q11微缺失的患儿,2例为3M典型缺失,1例为非典型缺失.结论 在先天性心脏病患儿中存在22q11微缺失.

Abstract：

Objective To detect 22q11 microdeletion in the children and fetuses affected by congenital heart defects.Method MLPA P250 kit was used to detect 22q1 1 microdeletion in 100 cases of sporadic congenital heart defects including 40 fetuses and 60 patients diagnosed by ultrasound.Result Two cases from the fetuses and 4 case from the patients were found to have 22q11 microdeletion.Conclusion Three cases had 22q11 microdeletion in the congenital heart defects.     

Mutation spectrum and clinical features of congenital long QT syndrome in 20 children: a single center study北大核心CSCD

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. © 2022 Chin J Pathol, June. All rights reserved.     

散发Rett综合征患儿新生MECP2突变亲源鉴定和X染色体失活15例分析

Objective Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females as sporadic cases due to de novo mutations in the methyl-CpG-binding protein 2 gene ( MECP2 ). Familial cases of RTT are rare and are due to X-chromosomal inheritance from a cartier mother. Recently, DNA mutations in the MECP2 have been detected in approximately 84.7% of patients with RTT in China. To explain the sex-limited expression of RTT, it has been suggested that de novo X-linked mutations oecttr exclusively in male germ cells resulting therefore only in affected daughters. To test this hypothesis, we have analyzed the parental origin of mutations and the XCI status in 15 sporadic cases with RTT due to MECP2 molecular defects. Methods Allele-specific PCR was performed to amplify a fragment including the position of the mutation. The allele-specific PCR products were sequenced to determine which haplotype contained the mutation. It was then possible to determine the parent of origin by genotyping the single nucleotide polymorphism (SNP) in the parents. The degree of XCI and its direction relative to the X chromosome parent of origin were measured in DNA prepared from peripheral blood leucocytes by analyzing CAG repeat polymorphism in the androgen receptor gene (AR). Results Except for 2 cases who had a frameshifi mutation; all the remaining 13 cases had a C→T transition mutation. Paternal origin has been determined in all cases with the C→T transition mutation. For the two frameshift mutations, paternal origin has been determined in one case and maternal origin in the other. The frequency of male germ-line transmission in mutations is 93.3%. Except for 2 cases who were homozygotic at the AR locus, of the remaining 13 cases, 8 cases had a random XCI pattern; the other five cases had a skewed XCI pattern and they favor expression of the maternal origin allele. Conclusion De novo mutations in sporadic RTr occur almost exclusively on the paternally derived X chromosome and that this is most probably the cause for the high female: male ratio observed in sporadic cases with RTT. Random XCI was the main XCI pattern in sporadic RTT patients. The priority inactive X chromosome was mainly of paternal origin.     

Clinical feature analysis of subdural effusion/hematoma after shunt use of adjustable valves in children with hydrocephalus北大核心CSCD

Objective To analyze the clinical data of children with hydrocephalus suffering from subdural effusion/hematoma after shunt(SEHS) with adjustable valves, and to provide reference for postoperative follow - up. Methods A total of 102 children with hydrocephalus treated with adjustable valves in the Department of Neurosurgery, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2017 to September 2021 were enrolled and studied retrospectively. There were 16 cases with SEHS, 11 of whom were male and 5 were female. The age ranged from 3 months to 13 years (median;2. 5 years). The age, clinical manifestations, the time of SEHS occurrence, treatment methods (pressure regulation only or combined with drilling and drainage), and prognosis of the patients were analyzed. The pressure adjustment treatment was to increase the by 10-20 mmH2O (1 mmH2O =0.0098 kPa) each time and the patients were followed up 2-4 weeks after the adjustment. If SEHS didn't improve according to the follow - up results, pressure regulation combined with drilling and drainage was recommended. Results Of the 16 patients with SEHS, 3 cases were over 3 years old, and the other 13 cases were 3 years old or below. Eleven cases were treated by pressure regulation only, and 5 cases who were all aged 3 years received pressure regulation combined with drilling and drainage. Symptoms occurred in 2 patients, including vomiting in 1 case, and head and limb shaking in the other case. Fourteen cases were asymptomatic. The time from shunt operation to the occurrence of SEHS was 1 month in 5 cases, who were all cured by pressure regulation only. SEHS occurred in 5 cases > 1-3 months after shunt surgery, and 2 cases of them were treated by pressure regulation combined with drilling and drainage. Three cases had SEHS > 3-6 months after shunt surgery, and 1 case of them was treated by pressure regulation combined with drilling and drainage. SEHS occurred in 3 cases more than 6 months after shunt surgery, and 1 case of them was treated by pressure regulation combined with drilling and drainage. For the patients who received pressure regulation combined with drilling and drainage, the time from shunt operation to the occurrence of SEHS was 1 month and 21 days, 2 months and 7 days, 4. 5 months, 7. 5 months, and 25. 0 months, respectively. The time from the occurrence of SEHS to the last reexamination with no SEHS detected was 1 month in 7 cases (all were cured by pressure regulation only); >1-3 months in 5 cases (3 cases were treated by pressure regulation combined with drilling and drainage); more than 3 months in 4 cases (2 cases were treated by pressure regulation combined with drilling and drainage). For the patients who received pressure regulation combined with drilling and drainage, the time from the occurrence of SEHS to the last reexamination with no SEHS detected was 1 month and 14 days, 2. 0 months, 3. 0 months, 7. 0 months and 8. 0 months, respectively. Except for 2 cases who experienced pressure regulating valve failure, all other cases were cured. Six cases were unilateral SEHS, and the SEHS volume was about 11 to 75 mL (median;39. 0 mL). Ten cases were bilateral SEHS, and the SEHS volume was about 23-380 mL (median; 158. 2 mL). The 6 cases were all cured by pressure regulation, and 5 cases of them had SEHS at the shunt tube insertion side. Conclusions SEHS in children with hydrocephalus is generally asymptomatic and rarely causes clinical symptoms. SEHS mostly occurs within 6 months after operation, especially within 3 months. SEHS found in 1 month after surgery can be cured by increasing the shunt valve pressure only. Therefore, SEHS can be cured by pressure regulation only by shortening follow - up and identifying SEHS early after shunt operation. This will also reduce the probability that patients require the drilling and drainage operation. © 2022 ＣｈｉｎＪＡｐｐｌＣｌｉｎＰｅｄｉａｔ. All rights reserved.     

Selective coronary angiography in follow - up and technical study of Kawasaki disease - induced giant coronary artery aneurysm北大核心CSCD

Objective To investigate the characteristics of long - term changes in giant coronary artery aneurysm (GCAA) caused by Kawasaki disease (KD) and the technical approach of using selective coronary angiography (SCAG) in children. Methods A retrospective analysis was made in 52 patients with KD and GCAA in acute phase, including 38 males and 14 females with an average age of (4. 1 ±2.5) years old ranging from 1 to 14 years old,from January 2008 to December 2018 at the Department of Cardiology, Guangzhou Women and Children's Medical Center. The selective coronary angiography (SCAG) was performed in the patients who were followed up for (10.6 ±3.6) years (1-19 years). The changes in coronary artery lesions were analyzed and the technical approach of SCAG was discussed in children. Results Among 52 patients investigated by SCAG, the location of coronary artery lesion was found the left - anterior descending branch in 21 cases(40.4%),20 cases(38. 5%) in the right coronary artery,8 cases (15.4%) in the left main trunk and 3 cases(5.7%) in circumflex. The left coronary artery in 2 cases and the right coronary artery in 4 cases were completely occluded,and collateral vessel formation was found in 12 cases. There were 21 cases of right coronary artery stenosis, including 7 cases of the right coronary artery occlusion and bridge - like neovascularization, and 4 cases of the right coronary artery woven lesions (thrombotic occlusion and clustered neovascularization). There were 27 cases of the left coronary artery stenosis with different degrees, including 5 cases of the left coronary artery occlusion and bridge - like neovascularization, and 2 cases of the left coronary artery woven lesions (thrombotic occlusion and clustered neovascularization). All of 52 patients with GCAA were followed up for 1 to 19 years. GCAA still existed in 40 cases. Regression to small coronary artery aneurysm was found in 8 cases,and mild - dilation regression was observed only in 4 patients. The resting electrocardiogram showed pathological Q wave and the left ventricular enlargement in 6 cases,and normal in the remaining 46 patients. The children had no subjective symptoms and their activities were not restricted.compared with SCAG,echocardiography detected 52 cases with proximal morphological changes in the coronary artery, but distal changes were found only in 3 cases. And 12 cases with coronary artery occlusion and neovascularization failed to be prompted by echocardiography. Conclusions GCAA induced by KD can persist for a long time, and has characteristics of coronary occlusion, stenosis, and collateral vessel formation. The conventional electrocardiogram and echocardiography are insensitive to the coronary artery morphology and dysfunction in KD sequelae. The SCAG is of great value in tracking this disease. For using SCAG in children,as long as the appropriate equipment and projection angle are selected, and the operation skills are mastered, satisfactory images and high success rate can be obtained. © 2019 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.     

Follow-up and prognosis analysis of rheumatic disease complicated with pulmonary arterial hypertension in children北大核心CSCD

Objective To explore the clinical features, follow-up characteristics and prognosis of rheumatic disease complicated with pulmonary arterial hypertension (PAH) in children, and to provide support for its clinical diagnosis and treatment. Methods A retrospective analysis was conducted on the data of rheumatic 24 patients complicated with PAH hospitalized in the Department of Rheumatology and Immunology, Children′s Hospital Affiliated to the Capital Institute of Pediatrics, Department of Rheumatology and Immunology, Jiangxi Children′s Hospital, Department of Pediatrics Ⅰ, the First Affiliated Hospital of Zhengzhou University and Department of Pediatrics, the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to June 2022.The rheumatic patients complicated with PAH were followed up by telephone on June 30, 2022, and their clinical symptoms, treatment, follow-up, and prognosis data were collected.According to different treatment methods, the patients were divided into different clinical subgroups. The change of PAH was analyzed. The t-test was used for comparison between groups.P<0.05 was statistically significant. Results A total of 24 cases were enrolled, with 7 males and 17 females.The average onset age of PAH was (10.97±3.79) years old.The median duration of PAH was 6.00 (32.20) months.The average pulmonary artery pressure was (51.71±17.66) mmHg(1 mmHg=0.133 kPa). There were 9 cases of systemic lupus erythematosus, 5 cases of Takayasu′s arteritis, 3 cases of juvenile dermatomyositis, 3 cases of undifferentiated connective tissue disease, 2 cases of systemic juvenile idiopathic arthritis, 1 case of Behcet′s disease, and 1 case of Kawasaki disease.Among 24 cases, the common symptoms were fever (14 cases), fatigue (10 cases) and dyspnea (7 cases). Of the 24 cases, 10 cases were complicated with hydropericardium, 9 cases with valve regurgitation, and 5 cases with decreased systolic and/or diastolic function.Lung changes were observed in 17 cases.Eleven cases were tested for B-type natriuretic peptide (BNP), and the BNP levels were all elevated in them (11 cases), with a median BNP of 3 073 (10 645) ng/L.After the first occurrence of PAH, 12 cases were treated with Methylprednisolone therapy, 10 cases received Cyclophosphamide therapy, and 2 cases who were both systemic lupus erythematosus, underwent blood purification.In the treatment of PAH, 11 cases were treated with pulmonary artery pressure reduction, and 7 of the 11 cases took PAH-targeted drugs.The mean decrease of the average pulmonary artery pressure in children receiving the targeted therapy[(44.80±24.08) mmHg] was significant higher than that in children not receiving the targeted therapy [(16.15±17.25) mmHg] (t=2.661, P=0.016). Twenty children were reexamined and/or followed up, and the average course of PAH at the telephone follow-up was (36.29±26.67) months.The pulmonary arterial hypertension in 6 cases completely recovered, with median recovery time of 8.00 (13.47) months, but 2 of them died after the complete recovery.The pulmonary arterial hypertension improved in 11 children, 1 of whom died and the remaining children were in stable condition.The pulmonary arterial hypertension worsened in 2 children, 1 of them improved previously but aggravated recently, and the other child did not monitor pulmonary artery pressure and died during telephone follow-up. Conclusions Rheumatic diseases complicated with PAH are rare and most often diagnosed in severe rheumatic children.It can lead to death, and is commonly accompanied by notably elevated BNP levels.The patients who have early PAH detection, intensive treatment of the primary disease, symptomatic and targeted pulmonary artery pressure reduction show a better prognosis. © 2023 Journal of Chinese Agricultural Mechanization. All rights reserved.     

中国Phelan-McDermid综合征1例患儿的临床及分子遗传学分析

目的 对1例不明原因的生长过快、发育迟缓患儿进行临床特征及基因诊断分析.方法 描述患儿临床特点;实验室检查采用常规G显带分析染色体核型,进一步通过多重连接依赖探针扩增(MLPA)对微小缺失片段进行拷贝数变异(CNVs)检测,同时应用比较基因组杂交芯片技术(array CGH)检测全染色体微小改变,并采用荧光原位杂交技术(FISH)对新发现的缺失片段进行实验验证.结果 1.患儿,男,1.5岁,宽额,尖下巴,生长过快,全面的发育迟缓,语言发育障碍、孤独症样表现.2.常规G带染色体核型示46,XY,MLPA结果显示患儿22q13段的SHANK3基因的9～23外显子及ACR、RABL2B基因的杂合性缺失,比较基因组杂交芯片分析证实22q13段杂合性缺失,并排除其他染色体的微改变,FISH进一步证实22q13段的缺失.结论 根据临床表现,结合各项实验室检查结果可诊断患儿为Phelan-McDermid综合征;针对性的CNVs适宜采用MLPA技术,而array CGH更宜作为全染色体CNVs的筛查.     

Therapeutic laparoscopy for superior mesenteric artery syndrome in 5 children: Treatment experience and lite-rature review北大核心CSCD

Objective To investigate the clinical characteristics and therapeutic laparoscopy treatment for superior mesenteric artery syndrome(SMAS) in children. Methods A retrospective study on 5 children with SMAS who failed to respond to the conservative treatment in the Second Hospital of Shandong University from March 2017 to March 2022 was carried out.All the patients underwent the laparoscopic lysis of the ligament of Treitz and duodenal lowering procedure.The clinical data were analyzed and literature retrieved from Wanfang and PubMed databases were reviewed. Results There were 3 boys and 2 girls in the 5 cases with SMAS.The average age was (12.4±1.4) years, and the preoperative body mass index was (15.2±0.8) kg/m2.The patients were admitted to the hospital with vomiting, abdominal pain and emaciation symptoms, and the duration of symptoms was (8.4±7.8) months.Gastroscopy, laparoscopic lysis of the ligament of Treitz and duodenal lowering procedure were performed successfully in all the patients, without conversions to open surgery.The average operation duration was (66.0±10.7) min.Food intake was allowed 1 day after surgery.Chylous fistula occurred 4 days after operation in one patient, whose symptom relieved after 11 days of conservative treatment.One patient still had nausea and vomiting symptoms 10 days after operation and was healed by knee-chest posture treatment.No other short-term complications were observed.The median postoperative duration of stay in the hospital was 7 (6-22) days.The patients were followed up for 9-56 (median: 21) months.All of them recovered well and gained weight.One patient had mild recurrent symptoms, and was cured after conservative treatment.A total of 15 literature on the treatment of SMAS by laparoscopic lysis of the ligament of Treitz was retrieved, and the cure rate was 40%-100%.Only one group of these cases had a cure rate below 75%. Conclusions The laparoscopic lysis of the ligament of Treitz and duodenal lowering procedure is safe, effective, simple and minimally invasive treatment for children with SMAS.It can be used as the first choice for most pediatric patients. © 2022 Chinese Journal of Applied Clinical Pediatrics. All rights reserved.     

Mucopolysaccharidosis Ⅶ:report of a case and renew of the literature

objective To investigate the clinical characteristics and diagnosis of mucopolysaccharidosis Ⅶ. Method The clinical and biochemical features of an infant with mucopolysaccharidosis Ⅶ confirmed by enzyme assay were analyzed.Result The 2 month-old male infant showed hydrops fetalis,mental retardation,coarse face,corneal clouding,hepatosplenomegaly,hernias,Alder-Reilly granules in the leucocytes and decreased platelet(32×109/L).The biochemical markers showed urinary glycosaminoglycans(GAG)(532.8 mg/L,controls＜70.0 mg/L).The ratio of GAG/creatinine was 161.3(controls:26.2±11.7).Serum chitotriosidase activity was 315.8 nmol/(ml·h) [control ＜53 mol/(ml·h)].Beta-glucuronidase activity was deficient in isolated leukocytes.Conclusion Severe form of mucopolysaecharidosis Ⅶ exhibited characteristics of hydrops fetalis.hepatosplenomegaly, coarse face,thromboeytopenia and Alder-Reilly granules in the leucocytes.The measurements of GAG in urinary and beta glucuronidase in leucocytes are critical to diagnosis and deferential diagnosis.     

Comorbidities in Down syndrome livebirths and health care intervention: an initial experience from the birth defects registry in Southern Thailand

Background:Down syndrome (DS) is the most common chromosomal disorder causing mental retardation with a worldwide average prevalence of 1-2 cases per 1000 births.This study aimed to determine the comorbidities associated with DS and the coverage of health care services and developmental interventions for DS iivebirths in Southern Thailand.Methods:A total of 149 livebirth DS infants,recruited through the prospective birth defects registry system during 2009-2013 in 3 provinces in Southern Thailand,were regularly followed-up every 3-6 months.The data collection form included the infants' demographic data,associated congenital anomalies,and developmental interventions.Results:The DS infants were born at an average gestational age of 38.5±2.3 weeks with average birth weight of 2760±478 g,length 48.5±2.2 cm,and head circumference 32.7±1.2 cm.Congenital heart diseases,gastrointestinal defects and congenital hypothyroidism were found in 43.0％,6.7％,and 12.1％ of the cases,respectively.The percentage of DS infants who received developmental interventions in this current study were significantly greater than in a previous study covering the years 1992-2002:early stimulation program 90.0％ vs.65.6％ (P＜0.01),and speech training program 74.8％ vs.38.9％ (P＜0.01),respectively,and the infants in our study began intervention programs significantly earlier,0.58±0.39 years vs.1.69±0.66 years,respectively.Conclusions:Congenital heart disease was the most common comorbidity associated with DS.The coverage of health care services and developmental interventions for DS children has generally improved in Southern Thailand.One hundred percent coverage of health services and interventions for children with special needs is expected in the near future.     

智力低下和孤独症男童脆性X基因突变的研究

目的应用改良基因检测方法,探讨脆性X综合征致病基因(fragileXmentalretardation"1,FMR1)在中国人群智力低下和孤独症中的作用。方法收集2002～2006年小儿神经、遗传代谢门诊诊断的男性孤独症患儿44例、非家族性智力低下男性患儿40例,建立适用于男性的FMR1基因突变检查方法,对检查阳性者以pfxa3探针进行Southern杂交。结果在44例孤独症患儿中,发现1例pfxa3杂交片段约0.2kb,为FMR1前突变;40例智力低下患者中FMR1基因未见异常。结论在孤独症人群中发现的1例FMR1基因前突变,其致病意义有待进一步阐明。     

Technique d’hybridation génomique comparative sur microréseau d’ADN et fœtopathologie

Microarray-based comparative genomic hybridization (aCGH) is becoming an efficient clinical diagnostic tool enabling genome-wide screening of segmental copy number variations (CNVs). Regarding its ability to detect segmental genomic CNVs in individuals with mental retardation, autism and multiple congenital anomalies, aCGH is gradually replacing cytogenetic methods. Using this tool as a prenatal test for foetal genomic imbalance offers the promise of detecting pathogenic gain or loss of genomic material more quickly and much more frequently than current methods. However, there is a concern about CNVs of uncertain significance (for example, predisposition to adult occurring disease with incomplete penetrance) which might lead to termination of normal pregnancies. We report in this article recent data using aCGH in foetuses from spontaneous or medically terminated pregnancies associated with multiple malformations. aCGH should be considered as a diagnostic tool to improve genetic counselling in fetopathology. We also report recent data on aCGH as a prenatal test. Larger studies with targeted arrays are mandatory to determine whether the improved overall detection rates of clinically chromosomal abnormalities will justify offering aCGH in a prenatal diagnosis setting.     

Autistic behaviour in Moebius syndrome

Seventeen children and young adults with Moebius syndrome were examined with a view to finding symptoms of autism. Some 40% of the group showed all or many of the symptoms typical of autistic disorder. The high frequency of autistic symptoms in Moebius syndrome might be a marked overrepresentation and could be suggestive of a common underlying neurobiological deficit at the brainstem level.     

Autistic Behaviour in Moebius Syndrome

ABSTRACT. Seventeen children and young adults with Moebius syndrome were examined with a view to finding symptoms of autism. Some 40% of the group showed all or many of the symptoms typical of autistic disorder. The high frequency of autistic symptoms in Moebius syndrome might be a marked overrepresentation and could be suggestive of a common underlying neurobiological deficit at the brainstem level.     

Magnetic resonance imaging of the brain structures in the posterior fossa in retarded autistic children

Midsagittal magnetic resonance images of the brains of retarded autistic children were compared to those of non-autistic mental retardation patients and controls. We found that the whole brain stem and particularly two of its components (the midbrain and medulla oblongata) were significantly smaller in retarded autistic children and mental retardation cases than in control children. The pons area was significantly smaller in mental retardation cases as compared to control children but did not differ between autistic and control children. Moreover, there was no difference in the brain stem between retarded autistic children and mental retardation cases. We also noted no difference in the cerebellar vermis area among retarded autistic children, mental retardation cases and control children. The ratio of the midbrain to posterior fossa area was significantly smaller only in autistic patients. Although the significance of these results is unknown, further examination of autistic children with a normal IQ is necessary.     

50例微缺失和微重复综合征患儿的临床表型及基因组拷贝数变异的分析

目的了解微缺失和微重复综合征(MMSs)的基因型与临床表型的关系及致病性拷贝数变异(CNVs)的发生机制。方法收集2013年6月至2015年9月,应用染色体微阵列(CMA)诊断为MMSs的患儿50例,总结分析其临床表现和致病性CNVs的特点。结果 50例MMSs患儿临床表现以精神发育迟滞(MR)、发育迟缓(DD)、矮小、特殊面容为主,且往往多系统的异常同时存在,共存在54处致病性CNVs,微缺失片段36个、微重复片段18个,片段大小介于28kb至48.5Mb,平均13.86Mb。致病性CNVs易发生在X染色体、15号染色体、1号染色体。结论 MMSs临床表现缺乏特异性,可以采取基因型优先的方法进行诊断。遗传方式、重组类型(缺失或者重复)、片段大小以及所包含的功能基因有利于新生突变CNVs的解读,少见发病机制的深入研究有望成为发现新的罕见MMSs的突破点。     

MLPA技术检测儿童ETV6/RUNX1~+急性淋巴细胞白血病基因拷贝数的变异

目的应用多重连接探针扩增技术(MLPA)检测在ETV6/RUNX1~+急性淋巴细胞白血病(ALL)患儿中基因拷贝数变异的情况,并与常规经典染色体核型分析及荧光原位杂交技术(FISH)检测进行比较,以评估MLPA技术的应用价值。方法回顾性分析2006年1月至2012年11月95例ETV6/RUNX1+ALL患儿的临床资料,包括临床特征、染色体核型检测结果及FISH检测结果。应用MLPA技术检测95例患儿中多个基因拷贝数变异的情况。结果 95例患儿中,73例(77%)检测到基因拷贝数的改变。每例患儿基因拷贝数变异个数的中位数为1(0~6)个。拷贝数变异率超过10%的基因为EBF1、CDKN2A/2B、PAX5、ETV6、RB1、BTG1。以上经MLPA技术检测到拷贝数变异的基因涉及的染色体片段在染色体核型检测中常检测不到改变。FISH技术检测ETV6基因拷贝数的结果与MLPA检测结果的符合率为66%。结论 MLPA可作为高效、简便的方法检测ETV6/RUNX1~+ALL患儿基因拷贝数的变异。     

孤独症儿童脆性位点精神发育迟滞1基因检测

目的对孤独症儿童进行脆性位点精神发育迟滞1(FMR-1)基因检测,探讨儿童孤独症与FMR-1基因的关系。方法孤独症患儿75例。用一般情况调查表进行调查,以儿童孤独症评定量表、孤独症行为检查量表筛查可疑患儿,按照中国精神障碍分类与诊断标准第3版(CCMD-3)的儿童孤独症诊断标准进行诊断和FMR-1基因检测。结果孤独症患儿FMR-1基因异常率极低,仅1.3%。结论儿童孤独症遗传学发病机制可能与FMR-1基因无关。     

Autism and attachment: a meta-analytic review

METHOD: Sixteen studies on attachment in children with autism were reviewed, and ten studies with data on observed attachment security (N = 287) were included in a quantitative meta-analysis. RESULTS: Despite the impairments of children with autism in reciprocal social interaction, the majority of the studies found evidence for attachment behaviours in these children. In four samples using the Strange Situation procedure the average percentage of secure attachments amounted to 53% (n = 72). Meta-analytic results showed that children with autism were significantly less securely attached to their parents than comparison children, and the combined effect size for this difference was moderate (r =.24). Children with autism displayed less attachment security than comparisons without autism, but this difference disappeared in samples with children with higher mental development, and in samples in which autism was mixed with less severe symptoms of autistic spectrum disorders. CONCLUSIONS: It is concluded that attachment security is compatible with autism, and can be assessed with Strange Situation type of procedures. The co-morbidity of autism and mental retardation appears to be associated with attachment insecurity.