目的:建立同步多色荧光原位杂交技术在外周血、羊水及单个胚胎细胞及骨髓细胞等样本中的实验方法,探索其在细胞遗传学、产前诊断、胚胎种植前诊断以及在血液病中的应用. 方法: 取外周血淋巴细胞、羊水细胞和不适于胚胎移植及冷藏的受精胚胎细胞、骨髓细胞分别制片,用相应的荧光标记的探针进行原位杂交,荧光显微镜取图分析. 结果:建立获得稳定可行的各类标本的实验方法. 结论:应用多色荧光原位杂交技术可对染色体进行快速准确的诊断,并可应用于产前诊断和胚胎种植前诊断及血液病的诊断.
作者：黎青；孙筱放；陈欣洁；孔舒；郑育红；黄艳仪 刊期： 2005年第01期
SUMMARY The Luteinizing hormone/chorionic gonadotropin receptor (LHR) plays a critical role in human male sexual development. Both gain-of-function and loss-of-function mutations of the LHR have been described. Gain-of-function mutations are dominant and cause constitutive activation of the receptor resulting in familial male-limited precocious puberty (FMPP). All activating mutations are single point mutations and are located in the transmembrane domain (TM). TM helix Ⅵ harbors the largest number of activating mutations with the codon of Asp-578 being the hot-spot of mutation. Besides causing abnormal sexual development, constitutively activated LHR may predispose an individual to the development of testicular neoplasia. The anti-thesis of FMPP is Leydig cell hypoplasia (LCH). This is caused by mutations that inactivate the LHR resulting in subnormal male sexual development or male pseudohermaphroditism. Inactivating mutations are recessive. The genetic cause of LCH is variable and there is no mutation hot-spot. Genotype-phenotype correlation can be identified in LCH with the milder form caused by mutated LHR with residual activity and the severe form caused by absence of signal transduction activity of the mutated receptor. Molecular diagnosis of the disorders caused by mutation of the LHR can be achieved by direct sequencing of the LHR gene.
作者： 刊期： 2005年第01期
作者： 刊期： 2005年第01期
SUMMARY Diagnosis of mitochondrial disorders has been difficult due to the clinical and genetic heterogeneity, as well as unique features of mitochondrial genetics. Definitive diagnosis requires the identification of molecular defects in either the mitochondrial or the nuclear genome. We describe the clinical and molecular characteristic of some common mitochondrial syndromes and molecular methodologies available for the detection of mitochondrial DNA mutations. This review provides overview of current molecular diagnosis of mitochondrial DNA disorders that is useful in patient care and genetic counseling.
作者： 刊期： 2005年第01期
SUMMARY Constitutional full trisomy 21 is a common disorder in which abnormal spermatogenesis has been previously described. However, constitutional mosaic trisomy 21 in an otherwise normal but infertile male has not been explored. We report a case with low level mosaic trisomy 21 in a non-syndrome but azoospermic patient. We also propose that the patient's azoospermia may be related to the constitutional mosaic trisomy 21 and thus resulting in a late onset of testicular failure.
作者： 刊期： 2005年第01期
作者： 刊期： 2005年第01期
SUMMARY Infantile (INCL, NCL1) and late-infantile (LINCL, NCL2) neuronal ceroid lipofuscinoses have been found to result from genetic deficiency of genes CLN1 and CLN2, respectively. The application of molecular analyses can facilitate prenatal diagnosis for families affected by NCL1 or NCL2, in which the familial mutation(s) have been identified. Molecular testing with allele-specific primer extension and DNA sequencing was performed in nine pregnancies, four from two NCL1 families and five from five NCL2 families. Lysosomal enzyme activity assays were carried out as well.Four fetuses from three pregnancies in NCL1 families were found to be carriers for a mutation 451C-T in the CLN1 gene and one was normal. Prenatal testing of three NCL2 families who carried mutation R208X in the CLN2 gene showed that all fetuses were carriers. In NCL2 families who carried either mutation IVS5-1C or/and IVS5-1A two normal pregnancies were detected. Our studies indicate that DNA testing, which may provide definitive prenatal diagnosis for NCL, may be used in combination with lysosomal enzyme activity analyses.
作者： 刊期： 2005年第01期
目的:分析影响儿童青少年的胰岛素敏感性的遗传和环境因素,并探讨其中体质指数(body mass index, BMI)、年龄和性别的作用.方法:选择5～18岁同性别双生子296对,平均年龄(12.4±3.5)岁,其中同卵双生子(MZ)223对,异卵双生子(DZ)73对.在DNA卵性鉴定基础上,应用Mx软件模型拟合分别计算BMI调整前后稳态模型胰岛素抵抗指数(homeostasis model assessment insulin resistance index, HOMA IR)和β细胞功能指数(HOMA β-cell function index,HBCI)的遗传度,并检验年龄和性别对于模型的作用.结果:HOMA IR与年龄、性别和BMI相关,HBCI与年龄相关,遗传分析HOMA IR、HBCI的模型为ACE,BMI调整前后HOMA IR男女生遗传度不同,HBCI无明显变化.调整后HOMA IR、HBCI遗传度分别为0.25、0.24.结论:儿童青少年人群中HOMA IR、HBCI受遗传和环境因素共同作用,环境因素的影响似乎更大;BMI是影响机体胰岛素敏感性的重要因素;年龄和性别对遗传度的影响可能不大.
作者：陈天娇；季成叶；逄增昌；杨业鹏；王伟；李红娟；胡永华 刊期： 2005年第01期
The International Conference of Medical Genetics 2004 (ICMG2004) was held at Peking University Health Science Center on July 14-18, 2004. This conference is a part of the series that have been organized by the North American Association of Chinese Medical Geneticists (NAACMG) and the Chinese Medical Genetics Association (CMGA) and was initialized by the year of 2000 at Nanjing (ICMG2000, Nanjing). The mission of the series is to promote research, education, and clinical practice on medical genetics in China as well as in south Asian countries. This year, more than 200 participants from Mainland China, Taiwan, Hong Kong, England, and United States attended the ICMG2004. The conference opened with a remark addressed by Dr. Qi-de Han, the Vice Chairman of the Standing Committee of National Congress, who is the Director of Peking University Health Science Center and the Executive President of Peking University. Dr. Owen Rennet, Scientific Director of NICHD, NIH, gave a keynote speech at the opening session. Six sessions, chaired by Drs. Virginia Anderson, Wai-Yee Chan, Tian-jian Chen, Jiang Gu, Jian Han, Tao-Sheng Huang, Marilyn Li, Gary Lu, Ming Qi, Bai-Lin Wu, Nanbert Zhong, Chun-Yan Zhou, have covered various aspects of medical genetics with focus on birth defect, which is different from the main focus of neurogenetic disorders at ICMG2000. These aspects include inborn error of metabolism, intervention of birth defects, prenatal diagnosis and newborn screening, chromosome abnormalities, molecular basis of genetic disorders, environmental factors and birth defects, and genetic counseling and clinical management.
作者： 刊期： 2005年第01期
目的:研究PAX6基因突变与脑结构异常的关系.方法:应用核磁共振成像技术,对一个由PAX6 c1080C→T突变引起无虹膜的家系中18名患者和6名正常人进行脑结构扫描.结果:该家系大部分PAX6基因突变患者表现出不同程度的脑质退化变性、胼胝体变薄萎缩和嗅球萎缩等脑结构的异常,其中有一例病人还表现出Chiari 畸形的影像学特征.结论:进一步证实了PAX6基因突变能够引起人脑结构异常.
作者：宋书娟；刘英芝；从日昌；张晓燕；杨振江；李凌松 刊期： 2005年第01期
核纤层蛋白病(laminopathies)是指由LMNA基因及其编码蛋白lamin A/C异常引起的一组人类遗传病[1].根据临床特征不同,至今被认识的核纤层蛋白病已有10种,除一种由影响成熟lamin A形成的FACE-1基因突变引起外[2],其余9种均由LMNA基因突变引起,其中包括2种既可以常染色体显性又可以常染色体隐性遗传的遗传病:Emery-Dreifuss 肌营养不良(Emery-Dreifuss muscular dystrophy, EDMD,常显EDMD2,常隐EDMD3)[3,4] 和腓骨肌萎缩症2型(Charcot-Marie-Tooth2,常显AD-CMT2,常隐AR-CMT2)[5,6];6种常染色体显性遗传病:肢带型肌营养不良1B(limb girdle muscular dystrophy1B,LGMD1B)[7],扩张性心肌病伴心脏传导阻滞1A(dilated cardiomyopathy and cardiac conduction defects1A, CMD1A)[8],家族部分性脂肪营养不良(familial partial lipodystrophy, FPLD)[9],脂肪营养不良、胰岛素抵抗型糖尿病、弥漫性白黑皮病样丘疹、肝脂肪变性和心肌病综合征(lipoatrophy & insulin-resistant diabetes & disseminated leukomelanodermic papules & liver steatosis and cardiomyopathy,LDHPC)[10],Werner综合征(Werner syndrome, WRN)[11]和早老症(Hutchinson-Gilford progeria syndrome,HGPS)[12];1种常染色体隐性遗传病: Mandibuloacral dysplasia(MAD)[13].
作者：宋书娟；章远志；Nanbert Zhong 刊期： 2005年第01期
目的: 研究北京地区1 200例汉族人群线粒体脂肪酸氧化代谢中的三功能蛋白酶(mitochondrial trifunctional protein,MTP)α亚单位的长链三羟基酰基辅酶A脱氢酶(long chain 3-hydroxyacyl-CoA dehydrogenase,LCHAD)G1528C基因的突变频率.方法: 应用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restricted fragment length polymorphism, PCR-RFLP)技术分析1 200例汉族正常产妇脐血MTP的α亚单位G1528C基因突变携带情况.实验以西方人种的G1528C杂合子标本为阳性对照,同时设立阴性和空白对照作为实验技术质控标准.结果: 1 200例汉族产妇脐血标本G1528C 基因经PCR-RFLP突变筛查检测后,未见有与阳性对照标本相对分子质量相同的条带出现.结论: 中国人群与白种人之间可能存在着种族差异,西方人种中常见的MTPα亚单位的G1528C基因突变可能不是中国人种中常见的突变位点.
作者：朱锦明；杨孜；余梅；王荣；叶蓉华；杨惠霞；翟桂荣；王琪 刊期： 2005年第01期
某些小的双链RNA可以高效特异地阻断体内特定基因表达,促使mRNA降解,诱使细胞表现出特定基因缺失的表型,称为RNA干扰(RNAi).RNAi同时也是体内抵御外在感染的一种重要保护机制.作为一种简单有效的代替基因敲除的遗传工具,RNAi将大大加速功能基因组学的研究进展,被Science评为2002年重要的科研成果之一.RNAi导致的基因沉默发生在转录后,所以被称为转录后基因沉默(PTGS).
作者：吴丹；吴白燕；梁红业；Nanbert Zhong 刊期： 2005年第01期
目的:了解MTHFR C677T、MS A2756G、MTHFD G1958A和CBS 844 ins68bp位点在中国北方正常人群中的基因型分布,并评价单一或复合位点基因变异与叶酸、维生素B12、同型半胱氨酸(Hcy)水平及先天性心胖病(CHD)的关系.方法:选择辽宁省192例CHD患者及其父母作为病例组,同一地区年龄、性别匹配的124名正常人及其父母作为对照组,采用PCR-RFLP方法检测其基因型,放射免疫法和荧光偏振免疫法测定血清叶酸、维生素B12和Hcy水平,比较两组差异.结果:中国北方正常人群中,这四个位点的突变等位基因频率分别为MTHFR 51.18%, MS 7.58%, MTHFD 24.32%, CBS插入频率 2.36%;CBS 844 ins68bp位点杂合型频率病例组明显高于对照组(子代为12.57% 和 2.97%, 父亲为10.88% 和 3.09%,母亲为11.54% 和 1.02%),子代的OR值为4.70 (95% CI 1.34～25.15),父亲的OR值为3.83 (95% CI 1.05～20.98),母亲的OR值为12.65 (95% CI 1.92～532.47),其他三个位点两组差异无统计学意义;MTHFR、CBS和MTHFD三个位点联合基因变异的母亲、MTHFR 和 CBS两个位点联合基因变异的母亲(OR=8.44,95%CI:1.23～362.26)、MTHFD 和 CBS两个位点联合基因变异的母亲在病例组中所占的比例明显高于对照组;病例组父亲和母亲的血清叶酸水平明显高于对照组;病例组母亲的血清Hcy水平高于对照组,但差异无统计学意义;MTHFR 和 MTHFD两个位点为纯合型者的血清叶酸和维生素B12水平轻微下降,而血清Hcy水平轻微上升;联合基因变异使血清叶酸、维生素B12和Hcy水平出现下降趋势.结论:这四个位点的基因多态性存在着种族和地区差异,CBS 844 ins68bp位点突变可能是CHD发生的一个危险因素,亲代(尤其是母亲)的插入突变可使其后代发生CHD的危险性升高.
作者：李勇；成君；朱文丽；刀京晶；闫丽盈；李孟忆；李书琴 刊期： 2005年第01期
作者： 刊期： 2005年第01期
SUMMARY Fluorescence in situ hybridization (FISH) has become an important diagnostic tool as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of specific nucleic acid sequences tagged with fluorescent molecules to identify the number and location of specific DNA sequences in human cells. These probes can be used to determine various numerical and structural chromosomal aberrations, in many cases, gene dosage and/or structure alterations. Chromosomal abnormalities are responsible for a considerable number of birth defects, and more than 50% of spontaneous abortions. These numbers have been significantly higher since the advent of FISH technology that allows the detection of submicroscopic chromosome alterations. The clinic application of FISH technology in postnatal, prenatal, and preimplantation diagnoses has been playing an important role in the diagnosis and prevention of birth defects. As new technologies evolve, more and more new FISH techniques - such as subtelomeric FISH, multicolor FISH (M-FISH), comparative genomic hybridization (CGH), and microarray - are used in clinical diagnoses, the role of FISH technology in both research and clinical aspects of birth defects will surely continue to expand.
作者： 刊期： 2005年第01期
Objective: To develop a molecular screening test for genetic defects on hearing loss related genes has significant impacts on early identification of hereditary hearing loss and genetic susceptibility to aminoglycoside ototoxicity. Early identification of pre-lingual hearing loss is very important for patient's language development, academic achievement, and social skill. Two common mutations, the 235delC in GJB2 gene and the mutation A1555G in mitochondrial DNA, are included in the newly developed screening panel for Chinese population. Methods: A molecular genetic assay, based on fluorescent labeled multiplex PCR and automatic DNA fragment analyzing techniques, was developed to detect both mutations simultaneously. Results: This assay was able to detect both mutations from patient's samples, and pooled DNA tests, as well as suitable to detect mutation from the DNA extracted from dried blood spot and buccal swab. Conclusion: This assay could be a useful tool for newborn screening and carrier screening for the hereditary hearing loss for the Chinese population.
作者： 刊期： 2005年第01期
SUMMARY Nephropathic cystinosis is a lethal inborn error of metabolism that destroys kidney function by age 10 years. It is characterized by lysosomal cystine accumulation. How the cystine causes the phenotype is an open question. We propose that during apoptosis, permeablized lysosomes permit cystine to reach the cytosol where mixed disulfide formation occurs, augmenting apoptosis by interaction with a variety of pro-apoptotic proteins.
作者： 刊期： 2005年第01期
目的:探讨微粒体环氧化物水解酶基因(microsomal epoxide hydrolase gene,EPHX1)139位点多态性和谷胱甘肽转硫酶theta1基因(the glutathione S-transferase theta1 gene,GSTT1)多态性对新生儿低出生体重的影响.方法:采用病例对照调查方法,使用统一设计的调查问卷,由经过培训的调查员于1998年至1999年在安徽省安庆市各县级医院对入院分娩孕妇及其单胎、活产的低出生体重儿和正常出生体重的对照新生儿进行调查,共得到246个母亲-新生儿对,其中低出生体重组73对, 正常出生体重对照组173对,用PCR-RFLP方法确定基因型.结果:EPHX1 His139His纯合子基因型与His139Arg杂合子基因/Arg139Arg纯合子基因型比较, GSTT1缺失基因型与存在基因型比较,多因素Logistic回归模型在经混杂因素(母亲年龄、文化程度、生育史、新生儿性别、孕周)调整前后,均未见导致低出生体重的危险性有显著性增加.进一步分析EPHX1139位点多态性和GSTT1位点多态性之间对低出生体重的影响,结果显示GSTT1缺失基因型和EPHX1His139His纯合子基因型之间有明显联合作用,导致低出生体重的危险因素增加(OR＝3.46, P=0.035).结论:基因EPHX1 139位点多态性和GSTT1位点多态性对低出生体重的影响有明显联合作用.
作者：梁红业；陈大方；张涛；杨帆；汪六六；陈栎；吴白燕 刊期： 2005年第01期
腓骨肌萎缩症也称为Charcot-Marie-Tooth病(CMT),是一类高发病率的周围神经系统单基因遗传病,可发生于世界范围的各个种族之中,发病率为1/2 500.遗传方式主要为常染色体显性遗传(AD),也可见常染色体隐性遗传(AR)及X连锁显性或隐性遗传(XD或XR).即使是同一家庭中的患者,其患病的严重程度也会不同.
作者：章远志；Nanbert Zhong 刊期： 2005年第01期
北京大学学报（医学版）杂志
主管:中华人民共和国教育部
主办：北京大学
