首页期刊导航|中华医学遗传学杂志
期刊信息/Journal information
中华医学遗传学杂志
四川大学
中华医学遗传学杂志

四川大学

张思仲

双月刊

1003-9406

cjmg@cma.org.cn

028-85501165

610041

四川省成都市人民南路三段17号(四川大学华西校区)

中华医学遗传学杂志/Journal Chinese Journal of Medical GeneticsCSCD北大核心CSTPCD
查看更多>>中华医学会主办，四川大学承办。本刊以报道我国医学遗传学、人类遗传学和相关领域的基础理论、技术方法等最新研究成果；以从事医学遗传学工作的各科临床医生、计划生育工作者、大专院校和科研单位有关人员为主要读者对象。设有述评、论著、技术与方法、综述、调查报告、遗传咨询、临床细胞遗传学、病例报告等栏目。 从1998年以来被美国《医学索引》（IM）、《化学文摘》（CA）、《工程索引》（EI）、ISI数据库的Biological Abstracts及BIOSIS Previews，波兰《哥白尼索引》（IC）,荷兰《医学文摘》（EM）和俄罗斯《文摘杂志》（AJ）等国际著名检索系统收录。
正式出版
收录年代

    染色体微阵列分析技术在产前诊断中的应用指南(2023) *

    刘俊涛张楠李岭
    1051-1061页
    查看更多>>摘要：2014年我国第1版关于染色体微阵列分析(CMA)技术应用于产前诊断的专家共识发布后，经过8年余临床和技术发展的推动，CMA技术目前已经成为针对胎儿的染色体拷贝数缺失或重复异常的一线产前诊断技术，广泛应用于我国产前诊断领域。但随着行业的发展和诊断经验的积累，CMA技术临床应用的许多重要方面，如临床诊断指征、数据分析和检测前后遗传咨询等亟须进一步规范和提升，以使CMA技术的产前诊断应用更加符合临床的需求。本次修订工作由国家卫生健康委员会妇幼健康司批准成立的全国产前诊断专家组牵头，委托北京协和医院等数家产前诊断机构进行初稿的撰写和讨论修订，并经全国产前诊断专家组全体专家进行研讨和审查反馈，以及广泛函审修改后最终形成本指南。本指南针对CMA技术在产前诊断临床应用的重要方面，包括临床应用指征、检测的质量控制、数据的分析解读、诊断报告撰写、检测前后遗传咨询等工作的规范开展进行了详细的阐述和介绍，完整体现了当前中国专家团队对于CMA技术产前诊断应用的经验集成、专业思考和指导意见。本指南的编制将推动全国胎儿染色体及基因组疾病产前诊断工作的规范性和先进性得到进一步的提升。 After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.

    染色体微阵列分析产前诊断指南

      原文链接:
    • 万方数据

    PGT-A患者不同活检日囊胚的染色体非整倍体情况及妊娠结局

    石森林石琼瑶姚桂东刘艳...
    1062-1067页
    查看更多>>摘要：目的 比较行胚胎植入前染色体非整倍体遗传学检测(PGT-A)患者的D5和D6囊胚的染色体非整倍体情况及妊娠结局。 方法 收集2018年9月至2020年9月在郑州大学第一附属医院生殖中心行PGT-A并进行解冻移植的268例患者的临床及实验室资料，比较D5和D6囊胚(分别为975个、710个)的染色体非整倍体情况及妊娠结局。 结果 D5囊胚的整倍体占比显著高于D6囊胚(49.1% vs. 41.1%，P＝0.001 1)，非整倍体的占比则显著低于D6囊胚(50.9% vs. 58.9%，P＝0.001 1)，其中D6囊胚染色体数目异常率显著高于D5囊胚(27.9% vs. 20.2%，P＝0.000 5)。>35岁者D5/D6囊胚整倍体和非整倍体率无差异，而≤ 35岁者D5囊胚整倍体比率显著高于D6囊胚(53.8%vs. 44.3%，P＝0.001)，非整倍体率则显著低于D6囊胚，且以染色体数目为甚(16.3% vs. 23.9%，P＝0.001)。无论D5还是D6囊胚，≤ 35岁者整倍体比率均显著高于>35岁者，非整倍体率均显著低于>35岁者，且均以染色体数目异常为主。高龄组囊胚整倍体比率与活产率最低。解冻移植D5囊胚的妊娠率(60.2%vs.37.0%，P＝0.000 3)、种植率(59.1% vs. 37.0%，P＝0.000 6)和活产率(47.7% vs. 28.3%，P＝0.002)均显著高于D6囊胚。 结论 对于PGT-A患者，D5囊胚整倍体比率高于D6囊胚，移植D5正常信号囊胚的临床结局优于D6囊胚；高龄患者非整倍体率高，且以染色体数目异常为主。 Objective To compare the prevalence of chromosomal aneuploidies and pregnancy outcomes of D5 and D6 blastocysts subjected to preimplantation genetic testing for aneuploidy (PGT-A). Methods Clinical and laboratory data of 268 couples who underwent PGT-A at the Reproductive Center of the First Affiliated Hospital of Zhengzhou University from September 2018 to September 2020 were collected. The prevalence of chromosomal aneuploidies and pregnancy outcomes of D5/D6 biopsied blastocysts were compared. Results Compared with D6 blastocysts, the euploidy rate of D5 blastocysts was significantly higher (49.1% vs. 41.1%, P=0.001 1), whilst their aneuploidy rate was significantly lower (50.9% vs. 58.9%, P=0.001 1). The rate of numerical abnormalities of D6 blastocysts was significantly higher than that of D5 blastocysts (27.9% vs. 20.2%, P=0.000 5). For patients under 35 years old, the euploidy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (53.8% vs. 44.3%, P=0.001), whilst the numerical abnormality rate was significantly lower (16.3% vs. 23.9%, P=0.001). For both D5 and D6 blastocysts, the euploidy rates for patients ≤ 35 were significantly higher than those for > 35. The elder group had the lowest rates for aneuploidies and live births. Compared with those receiving D6 blastocysts transplantation, the pregnancy rate, implantation rate and live birth rate for those receiving thawed D5 blastocysts transplantation were significantly higher (60.2% vs. 37.0%, P=0.000 3 59.1% vs. 37.0%, P=0.000 6 47.7% vs. 28.3%, P=0.002). Conclusion For patients undergoing PGT-A, the chromosomal euploidy rate for D5 blastocysts is higher than that for D6 blastocysts, and the clinical outcome of D5 blastocysts with normal signal is better than that of D6 blastocysts. Elder patients have a higher rate of aneuploidies.

    胚胎植入前染色体非整倍体遗传学检测非整倍体囊胚妊娠结局

      原文链接:
    • 万方数据

    精子发生障碍患者Y染色体 AZF区拷贝数变异的分析

    高慧王丽娟宋雅琴马迪...
    1068-1074页
    查看更多>>摘要：目的 探讨深圳地区精子发生障碍患者的Y染色体无精子因子(AZF)区域内的拷贝数变异(CNV)特征。 方法 选取2016年1月至2022年10月就诊于深圳市人民医院的123例精子发生障碍患者(73例无精子症患者，50例少精子症患者)及100例精液正常的男性为研究对象。应用多重连接探针扩增(MLPA)技术检测其AZF区，利用χ2检验或者Fisher确切概率法统计分析AZF区的CNV与男性精子发生障碍的关系。 结果 223例样本中共检出19种CNV，合计53例，其中无精子症中检出20例(27.40%，20/73)，少精子症中检出19例(38%，19/50)，正常对照组中检出14例(14%，14/100)。无精子症组、少精子症组及正常对照组中，AZFa区(含AZFab区与AZFabc区)相关的CNV检出率分别为5.48%(4/73)、2.00%(1/50)与0(0/100)；AZFb区(含AZFbc区)的检出率分别为6.85%(5/73)、0(0/50)与0(0/100)；AZFc区gr/gr缺失检出率分别为2.74%(2/73)、6.00%(3/50)、9.00%(9/100)；AZFc区b2/b4缺失检出率分别为2.74%(2/73)、10.00%(5/50)和0(0/100)；AZFc区复杂重排检出率分别为6.85%(5/73)、18.00%(9/50)和3.00%(3/100)；统计学分析显示，gr/gr缺失在三组间检出率差异无统计学意义(Fisher′s Exact Test值＝2.712，P＝0.249)；b2/b4缺失在三组间检出率差异有统计学意义(Fisher′s Exact Test值＝9.489，P＝0.002)，AZFc区复杂重排在三组间检出率差异有统计学意义(Fisher′s Exact Test值＝9.493，P＝0.006)。本研究还检出1例罕见的AZFa区ARSLP1基因缺失(涉及SY86缺失)的少精子症患者。 结论 AZFa区与AZFb区的CNV对男性的精子发生有严重影响，但AZFa区部分缺失(ARSLP1基因缺失)对男性的精子发生影响较小。AZFc区的b2/b4缺失与复杂重排可能为男性不育的风险因子。gr/gr缺失可能无法作为深圳地区男性不育的风险因子。 Objective To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. Methods A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People′s Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher′s exact test. Results 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher′s Exact Test value = 2.712, P=0.249) the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher′s Exact Test value = 9.489, P=0.002) the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher′s Exact Test value = 9.493, P=0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. Conclusion CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.

    精子发生长臂无精子症因子拷贝数变异多重连接探针扩增男性

      原文链接:
    • 万方数据

    长沙地区352 449例新生儿多种遗传代谢病的筛查结果分析

    李霞何玲孙玉亭黄旭镇...
    1075-1085页
    查看更多>>摘要：目的 回顾性分析长沙地区新生儿多种遗传代谢病的筛查情况，了解其单病种患病率及基因变异情况。 方法 对长沙地区2016年1月至2021年12月出生的352 449例新生儿进行串联质谱筛查，对筛查阳性者进一步行生化检测和基因变异分析以确诊。 结果 新生儿中初筛阳性6 170例，阳性率1.75%；召回5 437例，确诊92例，总体患病率为1/3 831，阳性预测值为1.69%。92例患儿共计检出18种遗传代谢病，包括氨基酸代谢病33例，其中苯丙氨酸羟化酶缺乏症20例，占60.60%；有机酸代谢病17例，其中2-甲基丁酰辅酶A脱氢酶缺乏症4例，占23.50%；脂肪酸代谢病42例，其中原发性肉碱缺乏症27例，占64.30%，短链酰基辅酶A脱氢酶缺乏症12例，占28.60%。基因分析共发现90种基因变异，最常见者为c.51C>G、c.1400C>G、c.760C>T、c.1031A>G和c.1165A>G。 结论 长沙地区新生儿遗传代谢病患病率较高者为原发性肉碱缺乏症、苯丙氨酸羟化酶缺乏症和短链酰基辅酶A脱氢酶缺乏症。本研究初步阐明了长沙地区遗传代谢病患儿的基因变异谱，有助于实现早期诊断及干预，提高出生人口的素质。 Objective To retrospectively analyze the screening results for genetic metabolic diseases among newborns from Changsha in order to determine the prevalence of single diseases and their mutational spectrum. Methods 352 449 neonates born from January 2016 to December 2021 in Changsha were subjected to tandem mass spectrometry. Suspected cases were further analyzed by biochemical and genetic testing. Results Among the 352 449 newborns, 6 170 were positive for the screening, which yielded a positive rate of 1.75%. 5 437 cases were recalled, and 92 were confirmed, with the overall prevalence being 1∶3 831 and positive predictive value of 1.69%. Eighteen genetic metabolic diseases were detected among the 92 children, including 33 amino acid metabolic disorder, among which 20 were phenylalanine hydroxylase deficiency (60.60%). 17 cases had organic acid metabolic disorders, among which 4 were 2-methyl-dehydrogenase deficiency (23.50%). 42 had fatty acid metabolic disorders, among which 27 (64.30%) were primary carnitine deficiency and 12 were short-chain acyl-CoA dehydrogenase deficiency (28.60%). In total 90 genetic variants were identified, with the most common ones including c. 51C>G, c. 1400C>G, c. 760C>T, c. 1031A>G and c. 1165A>G. Conclusion The common neonatal genetic metabolic diseases in Changsha include primary carnitine deficiency, phenylalanine hydroxylase deficiency and short-chain acyl-CoA dehydrogenase deficiency. The preliminary delineation of mutational spectrum for genetic metabolic diseases in Changsha can facilitate early diagnosis and intervention, so as to improve the quality of newborn population.

    遗传代谢病串联质谱新生儿筛查回顾性分析

      原文链接:
    • 万方数据

    甲基丙二酸血症伴同型半胱氨酸血症患儿65例的临床及 MMACHC基因变异分析

    陈重芬张耀东葛丽丽刘磊...
    1086-1092页
    查看更多>>摘要：目的 利用Sanger测序对65例甲基丙二酸血症伴同型半胱氨酸血症家系的MMACHC基因进行变异分析，总结其基因变异和临床特点及转归。 方法 以2017年4月至2022年4月于郑州大学附属儿童医院(郑州儿童医院)确诊的65例甲基丙二酸血症伴同型半胱氨酸血症患儿为研究对象，收集患儿的临床资料，并用PCR产物直接测序法对先证者及其父母的MMACHC基因进行变异分析。 结果 65例患儿年龄的中位数为3个月(14 d ~ 17岁)，来自新生儿筛查28例(43.08%)，有黄疸病史者11例(16.92%)，不同程度贫血者9例(13.85%)。临床症状以发育落后为主，其他包括增长缓慢、癫痫、脑积水、嗜睡、喂养困难、运动能力倒退或下降、反复呼吸道感染、贫血、黄疸、呼吸和心力衰竭、脑积水、肢体乏力、高血压等。血尿串联质谱筛查提示，甲基丙二酸、丙酰肉碱、丙酰肉碱/乙酰肉碱比值、丙酰肉碱/游离肉碱比值存在不同程度的升高，所有患儿的血同型半胱氨酸均存在升高。65例患儿的变异检出率为98.46%(128/130)，共检出22种MMACHC基因变异，最常见者为c.609G>A(W203X)(58/128)、c.658-660del(K220del)(19/128)和c.80A>G(Q27A)(16/128)，发现2种新变异：c.565C>T(p.R189C)、c.624_625delTG(p.A208Afs)，根据美国医学遗传学与基因组学学会(ACMG)相关指南分别判定为可能致病性变异(PM2_Supporting+PM3+PP2+PP3)和致病性变异(PVS1+PM2_Supporting+PM3+PP2)。变异频率最高的为第4外显子。 结论 MMACHC基因变异的检出明确了患儿的致病原因，其中c.609G>A变异出现频率最高。发现的2种新变异扩展了MMACHC基因的变异谱。 Objective To carry out Sanger sequencing for MMACHC gene variants among 65 Chinese pedigrees affected with combined methylmalonic aciduria and homocysteinemia, and summarize their genetic and clinical characteristics and prognosis. Methods Clinical characteristics of the 65 children identified with Methylmalonic acidemia and homocysteinemia at the Children′s Hospital Affiliated to Zhengzhou University (Zhengzhou Children′s Hospital) from April 2017 to April 2022 were selected as the study subjects. Potential variants of the MMACHC gene were detected by direct sequencing of the PCR products. Results The median age of the 65 children was 3 months (14 days to 17 years old). These included 28 cases (43.08%) from neonatal screening, 11 cases (16.92%) with a history of jaundice, and 9 cases (13.85%) with various degrees of anemia. The main clinical symptoms included development delay, slow growth, epilepsy, hydrocephalus, lethargy, feeding difficulty, regression or decline in motor ability, recurrent respiratory infections, anemia, jaundice, respiratory and heart failures, hydrocephalus, limb weakness, and hypertension. Blood and urine tandem mass spectrometry screening has revealed increase of methylmalonic acid, propionyl carnitine, propionyl carnitine/acetylcarnitine ratio, and propionyl carnitine/free carnitine ratio to various extents, and blood homocysteine was increased in all patients. The detection rate of genetic variants was 98.46% (128/130), and in total 22 types of MMACHC gene variants were detected. The most common ones have included c. 609G>A (W203X) (58/128), c. 658-660del (K220del) (19/128), and c. 80A>G (Q27A) (16/128). Two novel variants have been identified, namely c. 565C>T (p.R189C) and c. 624_ 625delTG (p.A208Afs), which were respectively predicted as likely pathogenic (PM2_Supporting+ PM3+ PP2+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PM3+ PP2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Exon 4 had the highest frequency for the detection. Conclusion Identification of MMACHC gene variants has confirmed the diagnosis in the children, among which the c. 609G>A variant has the highest frequency. Discovery of the new variants has enriched the mutational spectrum of theMMACHC gene.

    甲基丙二酸血症伴同型半胱氨酸血症MMACHC基因基因变异

      原文链接:
    • 万方数据

    Loeys-Dietz综合征12例的临床特征及基因变异情况分析

    范佳祺孙海瑞王欣武玉多...
    1093-1099页
    查看更多>>摘要：目的 对12例Loeys-Dietz综合征(LDS)患者的临床表征及基因变异谱进行总结分析，探讨LDS基因变异类型与临床表型的潜在相关性。 方法 选取2015年1月至2022年1月于首都医科大学附属北京安贞医院疑诊为LDS的12例患者为研究对象。收集患者的相关临床资料，提取患者外周血基因组DNA并进行基因检测，对候选变异进行致病性分析。 结果 12例LDS患者临床表型主要涉及心血管、骨骼肌肉、颅面、皮肤、眼部等多系统体征。4例患者(患者5-1、5-2、6、7)均携带TGFBR1基因杂合错义变异，5例患者(患者1-1、1-2、2、3、4)均携带TGFBR2基因杂合变异，2例患者(患者8-1、8-2)均携带TGFB3基因杂合移码变异，1例患者(患者9)携带SMAD3基因杂合错义变异。其中TGFBR1基因c.603T>G(p.1201M)及TGFB3基因c.536delA(p.H179fs35)变异均未见报道。 结论 LDS主要与TGFBR1、TGFBR2、SMAD3、TGFB2、TGFB3及SMAD2基因变异相关，同一变异位点所致疾病临床表型严重程度可能不一，不同变异位点所致疾病临床表型特异。 Objective To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. Methods Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. Results The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c. 603T>G (p.1201M) andTGFB3 c. 536delA (p.H179FS35) had not been reported previously. Conclusion Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.

    Loeys-Dietz综合征马方综合征主动脉夹层基因变异

      原文链接:
    • 万方数据

    SERAC1基因变异致MEGDEL综合征2例并文献回顾

    林晓霞林希严争陈燕惠...
    1100-1106页
    查看更多>>摘要：目的 探讨2例SERAC1基因变异所致的MEGDEL综合征患儿的临床表型及遗传学特点。 方法 以2020年7月14日与2018年7月28日就诊于福建医科大学附属协和医院儿科的2例MEGDEL综合征患儿作为研究对象。回顾分析患儿的临床资料及基因检测结果，并对MEGDEL综合征进行文献回顾。 结果 2例患儿均存在精神运动发育迟滞、肌张力障碍、感音神经性耳聋，尿3-甲基戊烯二酸升高，头颅MRI显示Leigh样综合征改变。全外显子组测序显示二者均携带致病性SERAC1基因复合杂合变异，分别为c.1159C>T、c.442C>T和c.1168C>T、第4 ~ 9外显子杂合缺失。 结论 SERAC1基因变异所致的MEGDEL综合征患儿临床表现多样，掌握其临床特点和典型的影像学改变将有助于提高临床诊治水平。尿有机酸检测联合基因变异分析有助于该病的早期诊断。上述发现丰富了SERAC1基因的变异谱。 Objective To explore the clinical phenotype and genetic features of two children with MEGDEL syndrome due to variants of the SERAC1 gene. Methods Two children who had presented at the Fujian Medical University Union Hospital respectively on July 14, 2020 and July 28, 2018 were selected as the study subjects. Clinical features and results of genetic testing were retrospectively analyzed. Results Both children had featured developmental delay, dystonia and sensorineural deafness, along with increased urine 3-methylglutaric acid levels. Magnetic resonance imaging revealed changes similar to Leigh-like syndrome. Gene sequencing revealed that both children have harbored pathogenic compound heterozygous variants of the SERAC1 gene, including c. 1159C>T and c. 442C>T in child 1, and c. 1168C>T and exons 4~9 deletion in child 2. Conclusion Children with MEGDEL syndrome due to SERAC1 gene variants have variable clinical genotypes. Delineation of its clinical characteristics and typical imaging changes can facilitate early diagnosis and treatment. Discovery of the novel variants has also enriched the spectrum of SERAC1 gene variants.

    MEGDEL综合征Leigh样综合征3-甲基戊烯二酸尿症SERAC1基因基因变异

      原文链接:
    • 万方数据

    苯丁酸甘油酯治疗鸟氨酸氨甲酰转移酶缺乏症2例的初步研究

    周朵商晓红乔玉程艺...
    1107-1112页
    查看更多>>摘要：目的 探讨苯丁酸甘油酯(GPB)治疗鸟氨酸氨甲酰转移酶缺乏症(OTCD)的有效性和安全性。 方法 选取2020年9月16日与2021年10月31日就诊的2例OTCD患儿为研究对象。观察2例OTCD患儿使用GPB治疗后的临床表现、血氨、肝酶、生长发育情况，结合文献检索分析GPB治疗尿素循环障碍的安全性和有效性。 结果 两例患儿经GPB治疗后，血氨和肝酶在3个月内均降至正常水平。患儿2的运动发育有所改善；患儿1出现一过性手心油脂味和食欲下降，未出现其他不良反应。文献分析显示GPB治疗期间患儿血氨总暴露量更低，高氨血症危象的年发生率降低，蛋白实际摄入量有所增加，不良事件减少。 结论 OTCD患儿应用GPB治疗安全有效。 Objective To evaluate the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy for patients with Ornithine transcarbamylase deficiency (OTCD). Methods Two children with OTCD were selected as the study subjects, and their clinical manifestations, blood ammonia, liver enzymes, growth and development information following the treatment with GPB were retrospectively analyzed. A literature review was also carried out by searching the PubMed database for studies on the GPB treatment for urea cycle disorders. Results With the GPB treatment, the blood ammonia and liver enzyme level in both patients have decreased to the normal range within 3 months. Motor development in child 2 has improved. No adverse reaction was noted, except for transient palmar greasy smell and loss of appetite in child 1. Analysis of the literature showed that patients had lower ammonia exposure, lower annual incidence of hyperammonemic crisis, more actual protein intake and fewer adverse events during GPB treatment. Conclusion GPB is safe and effective for the treatment of OTCD.

    鸟氨酸氨甲酰转移酶缺乏症尿素循环障碍苯丁酸甘油酯

      原文链接:
    • 万方数据

    FLT3基因的表达对于急性髓系白血病的调控作用初探

    唐思诗周燕虹周汶静王念...
    1113-1117页
    查看更多>>摘要：目的 从细胞实验和临床病例两个层面探讨FLT3表达对急性髓系白血病(AML)患者预后的影响。 方法 选取2012年1月至2017年6月就诊于四川大学华西医院的AML初诊患者为研究对象。构建FLT3过表达和干扰表达的AML细胞模型，检测促细胞凋亡基因BAK基因及蛋白表达水平，检测白血病细胞的增殖和凋亡情况。检测临床初诊的AML患者骨髓标本中FLT3的表达及FLT3-ITD变异，并随访患者的预后。 结果 细胞实验显示，FLT3过表达的AML细胞中BAK基因及蛋白表达水平均低于干扰表达组(P<0.001)，FLT3过表达的AML细胞增殖高于干扰表达组(P<0.001)，细胞凋亡率低于干扰表达组(P<0.001)。AML初诊患者FLT3表达水平高于健康对照(P<0.001)。FLT3-ITD阳性AML患者的FLT3表达水平显著高于野生型(P＝0.002)。生存分析结果显示，中风险组中FLT3高表达AML患者的完全缓解率及总体生存率低于低表达患者(P<0.001)。 结论 FLT3过表达可能通过促进白血病细胞增殖，抑制其凋亡从而影响AML的病程和患者的预后，可能是AML预后的不良因素。 Objective To assess the influence of FLT3 expression on the prognosis of patients with acute myeloid leukemia (AML) by cell experiment and clinical data analysis. Methods Models for FLT3 over-expression and interference-expression in AML cells were constructed. The level of BAK gene expression and its protein product was determined, along with the proliferation and apoptosis of leukemia cells. FLT3 gene expression and FLT3-ITD variant were determined among patients with newly diagnosed AML. Results Compared with the interference-expression group, the level of BAK gene expression and its protein in FLT3 over-expression AML cells was significantly lower (P < 0.001), which also showed significantly faster proliferation ( P < 0.001) and lower rate of apoptosis ( P < 0.001). The expression level of FLT3 gene among patients with newly diagnosed AML was also significantly higher compared with the healthy controls (P < 0.001). The FLT3 gene expression of FLT3-ITD positive AML patients was higher than that of FLT3-WT patients (P = 0.002). Survival analysis showed that AML patients with high FLT3 expression in the medium-risk group had a lower complete remission rate and overall survival rate compared with those with a low FLT3 expression (P < 0.001). Conclusion Over-expression of FLT3 may influence the course of AML by promoting the proliferation of leukemia cells and inhibiting their apoptosis, which in turn may affect the prognosis of patients and serve as a negative prognostic factor for AML.

    FLT3基因表达急性髓系白血病预后

      原文链接:
    • 万方数据

    多发性骨性连接综合征1型一个家系的表型及致病变异分析

    张文元毛璐张金慧许红恩...
    1118-1123页
    查看更多>>摘要：目的 探究1个多发性骨性连接综合征1型(SYNS1)家系的临床表型与致病性变异。 方法 选取2019年8月就诊于郑州大学第一附属医院儿科门诊的1个汉族SYNS1家系为研究对象。采集家系相关临床资料，提取各家系成员的外周血基因组DNA，进行全外显子组测序(WES)和全基因组测序(WGS)。 结果 该家系共3代14人，其中6人表现为传导性耳聋或混合性耳聋，同时合并近端指间关节粘连、鼻根宽平、鼻翼发育不良、弱视、斜视、短指、足趾分隔不全，与SYNS1的典型症状相符。WES未发现先证者及其父母存在NOG基因编码区致病性单碱基变异与插入缺失变异(InDel)，但是先证者及其母亲NOG基因及相邻基因区域存在大片段杂合缺失。WGS进一步确定先证者染色体17q22区存在约1.0 Mb杂合片段缺失(chr17：54171786_55143998)，该区域包含NOG基因。参照美国医学遗传学与基因组学学会(ACMG)相关标准与指南，该拷贝数变异(CNV)判定为致病性变异。 结论 NOG基因及其相邻区域的杂合缺失可能是该SYNS1家系的遗传学病因，丰富了中国人群的NOG基因变异和临床表型图谱。在常规测序方法未发现致病变异的SYNS1患者中，应对CNV进行分析。 Objective To explore the clinical and genetic characteristics of a Chinese pedigree affected with Multiple synostoses syndrome type 1 (SYNS1). Methods Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were carried out for the proband and her parents. Results The pedigree has comprised of 14 members from three generations, of whom six had manifested hearing loss, with other symptoms including proximal symphalangism, hemicylindrical nose, amblyopia, strabismus, brachydactyly, incomplete syndactyly, which fulfilled the diagnostic criteria for SYNS1. WES had detected no pathogenic single nucleotide variants and insertion-deletion (InDel) in the coding region of the NOG gene, whilst copy number variation (CNV) analysis indicated that there was a heterozygous deletion involving the NOG gene. WGS revealed a heterozygous deletion (54171786_55143998) in 17q22 of the proband. The CNV was classified as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion The heterozygous deletion in 17p22 involving the NOG gene probably underlay the pathogenesis of SYNS1 in this pedigree. Above finding has enriched the mutational spectrum of NOG. CNV should be considered when conventional sequencing has failed to detect any pathogenic variants in such patients.

    多发性骨性连接综合征1型NOG基因综合征型耳聋拷贝数变异

      原文链接:
    • 万方数据