孕妇，女，36岁，G2P1L1A1，已育一女，体健。平素月经规律，末次月经2020年3月10日，停经6 w时外院超声提示胚胎大小符合孕周，于孕11 w行颈项透明层(nuchal translucency，NT)测量，头臀长4.6cm，NT厚4.6mm，再次核实胎儿大小符合孕周。因NT增厚于一周后来济南市妇幼保健院产前诊断中心就诊，超声示头臀长5.7 cm，NT厚3.5 mm，胎儿大小符合孕周。于孕20 +3 w行超声检查：双顶径3.8 cm，腹围11.6 cm，股骨2.7 cm，颈后皮肤皱褶(nuchal fold，NF)厚0.63 cm(见图1)。既往体健，孕期无有毒有害物质接触史，否认家族遗传病史。夫37岁，体健，无不良嗜好，无不良接触史，夫妻双方非近期结婚。孕妇及家属经遗传咨询，同意行产前诊断并签署知情同意书。本研究经济南市妇幼保健院伦理委员会批准(2023-1-010)。
Objective:To observe the changing trend of abnormal karyotypes by analyzing the G-banding chromosome analysis results in children.Methods:The data of children who underwent G-banding chromosome analysis in Shenzhen Children’s Hospital from January 1, 2003, to December 31, 2021, were collected, the detection rate, type, and annual change trend of abnormal chromosome karyotypes of children in 18 years were summarized.Results:Among 13 709 selected children, 1 557 cases of chromosome abnormalities were detected, with a detection rate of 11.4%, and the majority of them were trisomy 21 (58.4%). For children born between 2001 and 2020, the chromosome abnormality rate and trisomy 21rate showed a downward trend.In 2008, the trisomy 21 detection rate fell below 10% for the first time. After 2016, the rate of trisomy 21remained stable at about 2.5%. Except for 2018, trisomy 21 is the most common abnormal chromosome karyotype; although the percentage of sex chromosome abnormalities fluctuated, there was no trend of decline or increase; the proportion of Turner syndrome was higher than or equal to that of Klinefelter syndrome.Conclusion:The chromosome abnormality of children in Shenzhen shows a downward trend both from the year of detection and from the year of birth, especially the decrease in trisomy 21.
Y chromosome short tandem repeats is one of the most commonly used genetic markers in forensic science. The "classical" stepwise mutation model (SMM) mostly considered as main mutation mechanism under of Y-STR mutation. With interpretation of some phenomena such as multi-allele pattern, multi-step mutation, and null allele, SMM doesn’t make sense. Non-stepwise mutation model includes non-allelic homologous recombination and gene conversion. Duplication and deletion are driven by NAHR to produce multi-allele pattern and genotype of null allele. The two-copy Y-STR loci underwent gene conversion, which changed the "heterozygous" typing to the "homozygous" type. Particular types produced by such non-stepwise mutation model can be observed in forensic science DNA database core and preference loci. It can also observe in father-son pairs and there are some distinctions in its geographic distribution. The kind of gene type can be used to identify and separate minor families from the main lineage in male family investigations. When determining tolerance step size and mutation rate investigation, it is important to take particular type and multi-step mutation caused by non-stepwise mutation model into account. Here, the non-stepwise mutation model and its resulting particular type and multistep mutation were reviewed. It provides a preliminary theoretical basis for better application in male lineage screening system.
Objective:To explore the genetic basis of a fetus with intrauterine growth retardation.Methods:Fetal amniotic fluid and peripheral blood samples were collected for G-banding karyotype analysis and single nucleotide polymorphism array (SNP-array) detection.Results:The chromosome karyotypes of the fetus and its parents were normal. SNP-array showed the fetus had carried 1.8 Mb microdeletion at 12p13.31, which was a new mutation. Ultrasonography showed intrauterine growth retardation.Conclusion:A prenatal diagnosis of fetus with 12p13.31 microdeletion induced intrauterine growth retardation was confirmed, which has provided guidance for her subsequent pregnancy.
孕妇1，35岁，G2P0。人工流产1次，此次妊娠在孕23 w系统B超提示：胎儿先心病(B型主动脉弓断离、室缺)。既往体健，否认遗传病及传染病史，否认宠物接触史，否认感冒发烧病史，否认其他有毒有害物质接触史，否认家族遗传病史。
孕妇，32岁，G3P1，人工流产1次，4年前剖腹产一男婴，体健。家庭养狗，TORCH阴性。夫妻双方表型智力正常，无有毒有害物质接触史、遗传病及传染病史。所有检测均由孕妇及家属签署知情同意书。本研究符合《世界医学协会赫尔辛基宣言》。
孕妇1，30岁，G2P0，第1胎胎儿头围小(－3.79SD)、前额扁平(额鼻角增大约140°)，行羊水染色体微阵列分析(chromosome microarray analysis，CMA)检查未见明显异常，后胎儿死胎引产。第二胎孕29 w超声检查发现头围小，双顶径66 mm(－2.43SD)，头围247 mm(－2.27SD)，股骨53 mm，腹围237 mm，马蹄肾(峡部厚约12 mm)。孕32 +4 w超声提示双顶径77 mm(－1.64SD)，头围267 mm(－3.20SD)，股骨62 mm，腹围275 mm，马蹄肾(峡部厚约7.2 mm)，见图1。
Objectives:To provide prenatal diagnosis and genetic counseling for women with screening indication of fragile X syndrome(FXS) and their families by screening and summarizing the distribution of (CGG)n repeats number in FMR1 gene among pregnant women with screening indication of FXS and males with unexplained mental retardation. Methods:For 271 pregnant women with screening indication of FXS and 29 males with unexplained mental retardation, the (CGG)n repeats of the FMR1 gene were analyzed by FragilEase? PCR. Prenatal diagnosis was provided to carriers of pre-mutation and full-mutations. Results:We found that the most frequent (CGG)n repeats allele was 30 repeats (128/542) in pregnant women with screening indication of FXS and 32 repeats (5/29) in males with unexplained mental retardation. Among 271 pregnant samples, 3 gray zone repeats carriers and 1 pre-mutation carriers (one mosaic with pre-mutation and full-mutation) were detected, which gave a prevalence of 1.11% and 0.37%, respectively. Among 29 male samples, 2 full-mutation carriers were detected (a prevalence of 6.89%). Prenatal diagnosis and genetic counseling were provided for all families involved in this study.Conclusions:FRM1 gene testing in women with screening indication of FXS and in males with unexplained mental retardationcan facilitate prenatal diagnosis and reproductive guidance for carriers of gray zone repeats and pre-mutations. Accurate genetic counseling for carriers of pre-mutation would assist reduction of the birth of children with FXS.
病例1：孕妇28岁，G1P0，妊娠17 +3 w行超声检查示：NT 5.3 mm，单脐动脉，遂来济南市妇幼保健院就诊，要求羊水产前诊断。夫妻均适龄结婚，否认遗传病家族史(见图1)。
患儿，女，11岁，2022年6月下旬无明显诱因出现乏力、纳差，伴右侧髂骨疼痛，未重视。2022年7月10日起乏力进行性加重，就诊于定西市某三甲医院。查血常规(7月11日)：白细胞计数(white blood cell，WBC)为18.29×10 9/L，血红蛋白(hemoglobin，HGB)为35 g/L，血小板(platelet，PLT)计数为10 6×10 9/L。外周血涂片：原始细胞占总数的12%。骨髓细胞形态学：骨髓象增生明显活跃、原始细胞占总数的17.5%，可见Auer小体。免疫分型：可见约15.4%的髓系原始细胞伴免疫表型异常，表达CD34、CD13、CD33、CD117，部分表达HLA-DR，不表达CD2、CD3、CD5、CD7、CD8、CD10、CD11b、CD14、CD15、CD16、CD19、CD20、CD56、CD64。粒细胞相对比例正常，其免疫表型CD16、CD13、CD15、CD11b可见明显表达紊乱。56种白血病融合基因筛查： WT1阳性。给予成分血输注、对症治疗。
With the popularization of newborn screening, the incidence rate of congenital hypothyroidism(CH) is increasing year by year. Through the study of its genetic etiology, it has been found that some genetic syndromes caused by gene mutations are clinically manifested as congenital hypothyroidism. However, there is currently insufficient understanding of such syndromes in China, which can lead to missed diagnosis or delayed treatment, and may lead to disease progression and adverse prognosis. This article reviews the genetic syndromes related to congenital hypothyroidism, in order to enhance clinicians’ understanding of such syndromes and contribute to further study by domestic scholars on the genetic mechanisms of congenital hypothyroidism.
患儿，男，12岁，因语言智力发育迟缓就诊。患儿系足月顺娩，出生体重3 700 g，出生反应可，喂养可。1岁时不会趴，不会独坐。2岁7个月曾于山东大学齐鲁儿童医院就诊，脑电图提示：各导联阵发尖慢、棘慢综合波；双侧额极、额区阵发棘慢综合波。4岁时曾于首都儿科研究所附属儿童医院就诊，脑电图提示：睡眠期双侧额极、额、中央、前颞各导联可见稍多量单发棘波、棘慢波、多棘波、多棘慢波。磁共振示：双侧大脑半球额叶容积较小，脑白质容积少，印象：额叶发育落后。脆性X综合征检测提示正常。其母亲自诉曾于当地医院康复治疗，效果欠佳，4岁后未再就诊，患儿无典型癫痫发作，偶有严重哭闹。现其母亲有再次生育要求，于济南市妇幼保健院产前诊断中心就诊，查体：患儿无明显特殊面容，身高150 cm，体重42 Kg，目前可独走，不会成句说话，大运动及精细运动仍欠佳，生活不能自理。母亲34岁，健康，G1P1。父亲36岁，健康。否认家族中有类似病例及相关遗传病史，否认近期结婚。
患儿，男，3岁，以"双下肢无力伴血尿1 d"为主诉入院。1 d前患儿物明显诱因出现双下肢无力，站立不稳，休息后无缓解，夜间出现浓茶色尿，就诊于当地医院，化验提示"丙氨酸转氨酶(alanine transaminase，ALT)494.9 U/L，天冬氨酸氨基转移酶(aspartate transaminase，AST)2 505.8 U/L，肌酸激酶16 576.0 U/L，肌红蛋白>3 000 ng/mL，尿红细胞3+，尿蛋白2+"，遂转至西安交通大学附属儿童医院。患儿近期无剧烈运动史及药物误服史，精神状态良好，体温正常，饮食、睡眠及大便正常。
患儿，女，系母G1P0，足月因"羊水少"行剖宫产娩出，出生体重2.4 Kg。母乳喂养，未添加辅食。患儿2月龄及4月龄时均因"支气管肺炎"住院治疗5~7 d。3月抬头，5月翻身，可咿呀发音。5月24天，以"间断发热伴呼吸急促5 d"入西安市儿童医院。5 d前患儿无明显诱因出现发热，体温达39.0 ℃，伴有呼吸急促，当地医院予静滴"头孢曲松"抗感染治疗1 d，疗效欠佳，仍反复发热伴咳嗽，予"美罗培南"抗感染治疗4 d，患儿体温好转，但呼吸急促进行性加重，伴有呻吟、面色及口周发绀，遂就诊于西安市儿童医院，以"支气管肺炎、呼吸衰竭"收入儿童重症医学科。发病以来，患儿精神食纳差，大小便正常。父母体健，否认近亲结婚，否认家族遗传病及类似疾病史。
患儿，男，2月9天，G1P1，足月顺产，出生体重2.9 Kg，出生时无窒息。以"呼吸急促伴面色苍白1 d"入西安市儿童医院。1 d前患儿无明显诱因出现呼吸急促、烦躁不安，同时伴有面色苍白，无发热，无呕吐、腹泻，就诊当地医院，予布地奈德雾化、维生素K1及抗感染等对症治疗，症状无明显改善，后转诊至西安市儿童医院。病程中呼吸急促、面色苍白，查血常规提示血红蛋白20 g/L，予气管插管后转入儿童重症监护病房，发病两周以来患儿偶有咳嗽、呛奶，精神欠佳，无呕吐、腹泻，无皮疹，无抽搐，大小便正常。既往无特殊病史，无食物、药物过敏史。按时计划免疫接种。混合喂养，生长发育同正常同龄儿。父母体健，否认近亲结婚，否认家族遗传病及类似疾病史。
Objective:Pancreatic adenocarcinoma (PAAD) is one of the more malignant tumors of the digestive system with a poor prognosis. The aim of this study was to investigate the clinical significance and analyse the relationship between lactate metabolism genes and the tumor microenvironment.Methods:Pancreatic cancer and non-lesioned pancreatic cancer data were downloaded from the TCGA and GTEx databases, respectively, and lactate metabolism genes were downloaded from the GeneCards database. Lactate metabolism genes were identified as PAAD differentially expressed lactate metabolism genes and then prognostic models for pancreatic cancer lactate metabolism genes were constructed by univariate and LASSO-Cox methods. ssGSEA and ESTIMATE algorithms were used to assess the lactate risk gene relationship with the tumor microenvironment.Results:The prognostic model consisting of seven key lactate genes ( UCA1, ARNT2, PNPLA6, ATP6V0A1, MET, PRPF8, KRT7) is of great clinical value in independently predicting the prognosis of PAAD patients. In the tumor microenvironment, a variety of immune cell infiltrates showed a suppressed state in the group at high risk of lactate metabolism, including NK cells, regulatory T cells and eosinophils. Conclusion:The prognostic model of PAAD constructed through lactate metabolism-related genes and analysis of the tumor microenvironment provide new evidence for the prognosis and clinical treatment of patients with PAAD.
miRNA-205 is a relatively conserved endogenous non-coding small molecule RNA. Previous studies on miRNA-205 have focused on the development and progression of tumor diseases. In recent years, it has been found that abnormally expressed miRNA-205 can be involved in the pathological and physiological processes of cardiovascular and respiratory diseases affecting disease progression. miRNA-205 is an important clue for the diagnosis and treatment of these diseases in cardiovascular and respiratory diseases. This paper reviews the pathophysiological processes of miRNA-205 in different cardiovascular and respiratory diseases, and discusses the potential of miRNA-205 in the diagnosis and treatment of cardiovascular and respiratory diseases as well as the research progress.
患者(Ⅱ-2)，女，34岁，G5P4，2012年孕31 w顺产1男婴，出生窒息，抢救无效，当日夭折，产前B超提示羊水多；2014年因"高血压"剖宫产1女婴，现体健；2017年孕35 +6 w因"胎儿宫内窘迫"剖宫产分娩1男死婴；2018年人流1次；2021年孕37 w因"前两次剖宫产、羊水过多"于医院剖宫产娩出1男婴(Ⅲ-5)，出生无呼吸，全身肌张力低下，复苏后，仍持续依赖呼吸机辅助通气，出生4 d家属坚决放弃治疗，撤离呼吸机后夭折。患者欲再生育，就诊至西北妇女儿童医院，就诊时患者姐姐(Ⅱ-1)孕22 w。夫妇均体健，否认近亲婚配。双方家族史无特殊可记，家系图见图1。
Objective:To investigate the clinical screening efficacy of extended non-invasive prenatal screening (NIPT-plus) in elderly pregnant women.Methods:A retrospective analysis of 1 435 elderly pregnant women (≥35 years) receiving NIPT-plus at Northwest Women’s and Children’s Hospital from October 2021 to July 2022.Analyze the NIPT-plus results and simultaneously classifying the detected fetal chromosomal abnormalities. We also calculate the proportion of chromosomal abnormalities. The results were verified by amniotic fluid cell chromosomecopy number variation sequencing(CNV-seq). The positive rate, sensitivity, specificity, positive predictive value, negative predictive value of the test data compared with the NIPT-plus results. Telephone follow-up for pregnancy outcomes.Results:1 435 elderly pregnant women with high risk included autosomal trisomy and sex chromosome aneuploidy (sex chromosome aneuploidies, SCAs), microdeletion/microduplication syndrome(MMS), additional chromosome copy number variations (copy number variations, CNVs) were 2.9% (41 / 1 435). Among 41 cases with high risk of NIPT-plus, 8 cases refused invasive prenatal diagnosis; There were 16 cases with prenatal diagnosis results consistent with NIPT-plus results and 17 inconsistent cases, of which 14 cases had no detectable NIPT-plus screen-detected positive results and 3 cases detected other chromosomal CNVs that differed from the positive results detected by the NIPT-plus screen. The positive predictive value of NIPT-plus for fetal 21-trisomy, 18-trisomy, sex chromosome abnormalities, the additional CNVs was 100%, 100%, 66.67%, 40% respectively.Conclusion:This study obtained PPV data and pregnancy outcome follow-up of chromosome aneuploidy, MMS and additional CNVs for NIPT-plus in elderly pregnant women screening; When NIPT-plus screening suggests suspicious chromosome abnormalities, further invasive prenatal diagnosis is required to provide a reliable basis for clinical genetic consultation and dealing with the results of NIPT-plus screening in elderly pregnant women. NIPT-plus screening should be carried clinically out and popularized. It is necessary for elderly pregnant women to implement the mode of NIPT-plus screening before invasive prenatal diagnosis.
Pulmonary fibrosis is a fatal disease with poor prognosis. Its pathogenesis is still unclear and there is no effective treatment nowdays. The sirtuin family, a kind of deacetylase, is closely related to various physiological and pathological processes such as genome stability, aging, inflammation, oxidative stress, apoptosis, autophagy and fibrosis etc. In this paper, the role and mechanism of sirtuin family members in pulmonary fibrosis was reviewed, in order to provide scientific data for clearing the pathogenesis and seeking effective therapeutic measures of pulmonary fibrosis.
