328例非特异性精神发育迟滞的隐性基因分析

采用分离分析和血缘分析方法，对山东省遗传病调查中发现的３２８个父母双方均正常的中、重度非特异性精神发育迟滞（ＮＳＭＲ）家系进行了分析。结果表明，多发家庭先证者的平均近婚系数显著高于一般群体，分离比接近０．２５。提示隐性基因在中、重度ＮＳＭＲ发生中起一定作用。在重度ＮＳＭＲ，散发病例占４０．７％，Ｘ连锁隐性遗传占９．１２％，常染色体隐性遗传占５０．１８％。常染色体隐性基因位点数的最小估计值为２４，各位点的平均基因频率为０．００３５，携带者总频率为１７．５４％；在中度ＮＳＭＲ，散发病例占６１．５％，Ｘ连锁隐性遗传占１１．５３％，常染色体隐性遗传占２６．９７％，常染色体隐性基因位点数的最小估计值为１３２，各位点的平均基因频率为０．００２１，携带者总额率为５４．９５％。     

X－连锁智力低下

Ｘ－连锁智力低下山东医科大学附属医院围产医学中心（２５００１２）王济周Ｘ－连锁智力低下（ＸＬＭＲ）在小儿智力低下（ＭＲ）中占２５％～５０％，男性多见，在男性中发病率为０．１８３％，女性携带者率为０．２４４％，Ｘ－连锁位点的畸变率在３～９×１０－５。据...     

非特异性X连锁智力低下(MRX46)基因定位在Xq25-q26

Ｘ连锁智力低下 (ＸＬＭＲ)是男性智力障碍中最常见的。Ｘ染色体基因突变可以解释智力低下全部病例的 2 5% 50 %。大约有 10 0多种ＸＬＭＲ是属于可识别的综合征。另外智力障碍并不与表型特征相一致 ,被认为是非特异性ＸＬＭＲ或ＭＲＸ。ＭＲＸ家系的连锁分析明确显示了在Ｘ染色体上有 50多个位点簇集在 8个非重叠的区域。其中包括ＦＲＡＸＥ智力低下基因和ＫＡＢ ＧＤＪ基因 ,提示10种非特异性智力低下Ｘ连锁基因的最小值。本文报道了非特异性连锁智力低下的一个大家族 ,并定位在过去极少与ＭＲＸ相联系的Ｘｑ2 5 ｑ2 6。并将遗传性的致病…     

用RT-PCR技术分析脆性X男性患者的FMR-1基因的表达

目的为探讨脆性Ｘ男性患者与ＦＭＲ－１基因表达之间的关系，从而建立一种快速、简单且适合于筛查群体中男性患者的方法。方法采用ＲＴ－ＰＣＲ技术，对两个经细胞遗传学方法证实的脆性Ｘ家系进行检测。结果两个脆性Ｘ家系中的男性患者均无ＦＭＲ－１基因的表达，其父母均有ＦＭＲ－１基因表达，所有被检个体均有内对照基因ＨＰＲＴ的表达。结论ＦＭＲ－１基因表达缺失与脆性Ｘ男性患者的发病有一定关系。这一方法的进一步研究，将使脆性Ｘ男性患者的诊断方法更加简单、快速，有可能用于大规模群体筛查。     

Smith-Fineman-Myers综合征基因定位于Xq25

目的　定位 Ｓｍｉｔｈ Ｆｉｎｅｍ ａｎ Ｍｙｅｒｓ 综合征基因,为分离该基因奠定基础。方法　应用覆盖 Ｘ染色体全长的、具有多态性的短串联重复序列（ Ｓ Ｔ Ｒ） 对 Ｘ 染色体进行扫查,确定致病基因所在区域和与致病基因连锁的 Ｓ Ｔ Ｒ 位点,再对该位点两侧的 Ｓ Ｔ Ｒ 位点进行分析,确定致病基因的精确位置。结果　用２０个覆盖 Ｘ 染色体全长的、具有多态性的 Ｓ Ｔ Ｒ 位点对该综合征患者家系中的１３ 个能明确提供连锁分析信息的家系成员进行分析,发现位于 Ｘｑ２５ 上的 Ｄ Ｘ Ｓ１００１ 与致病基因紧密连锁,最大两点ｌｏｄｓ 得分为３０１（θ＝ ０） ,对 Ｄ Ｘ Ｓ１００１ 两侧的 Ｓ Ｔ Ｒ 分析证实,该致病基因位于 Ｄ Ｘ Ｓ１００１ 区域,单体型分析表明该致病基因位于 Ｄ Ｘ Ｓ８０６４ 和 Ｄ Ｘ Ｓ８０５０ 之间,区域为１４６ｃ Ｍ。结论　 Ｓｍｉｔｈ Ｆｉｎｅｍ ａｎ Ｍｙｅｒｓ 综合征基因,位于 Ｘｑ２５ 上的 Ｄ Ｘ Ｓ８０６４ 和 Ｄ Ｘ Ｓ８０５０ 之间的１４６ｃ Ｍ 区域,该基因的定位为分离该基因奠定了基础。     

性反转综合征患者SRY基因的初步分析

应用聚合酶链反应（ＰＣＲ）结合限制性酶谱分析对１０例性反转综合征患者的外周血ＳＲＹ基因进行了研究。结果显示：６例４６，ＸＹ与女性和３例４６，ＸＸ男性均有ＳＲＹ基因存在，另１例４６，ＸＸ男性无ＳＲＹ基因；６例４６，ＸＹ女性ＳＲＹ基因ＰＣＲ产物ＭｓｐＩ和ＴａｑⅠ限制性酶谱分析未发现异常。为性反转综合征的病因学研究提供了资料。     

通过精子分型测定FMR1CGG重复间断对突变频率的影响

脆性Ｘ综合征是一种低外显率的Ｘ连锁显性疾病，智力低下是常见的临床表现，其分子学基础为Ｘｑ２７．３的ＦＭＲ１等位基因功能丧失，这是由于ＦＭＲ１基因５′端非翻译区ＣＧＧ重复扩展的结果。脆性Ｘ综合征起源于ＦＭＲ１基因的ＣＧＧ重复不稳定表达。目前已识别出３种...     

男性弱智群体脆性X综合征全突变者的筛选研究

男性弱智群体脆性Ｘ综合征全突变者的筛选研究李薇杜风兰朱丽阳荆泽李军脆性Ｘ综合征是Ｘ－性连锁先天性智力低下中最常见的一种疾病。１９３１年Ｖｅｒｖｅｒｋ等［１］应用分子克隆技术发现了在Ｘｑ２７．３脆性位点附近的智力低下基因（ＦＭＲ－１），揭示该综合征的发...     

IL—2R缺陷所致X—性联严重联合免疫缺陷病及其基因治疗

人体白介素－２受体γ是链组成中，高亲和力ＩＬ－２Ｒ的重要成员，其基因已被定位于Ｘｑ１３区。遗传学连锁分析提示ＩＬ－２Ｒγ链基因与Ｘ－性联严重免疫缺陷病位点存在于同一位置，并发现Ｘ－ＳＣＩＤ患者扔ＩＬ－２Ｒγ链基因存在突变，从而证明了Ｘ－ＳＣＩＤ与ＩＬ－２Ｒ的γ链缺陷有关。     

中国人2型糖尿病的基因分型和定位

目的　对中国人２ 型糖尿病即非胰岛素依赖型糖尿病（ＮＩＤＤＭ）家系基因组ＤＮＡ进行基因分型及基因定位。　方法　采用分布于１～２２ 号染色体及Ｘ染色体上的３５８ 对荧光标记的微卫星引物,进行多重ＰＣＲ,ＰＣＲ扩增产物用聚丙烯酰胺凝胶电泳（ＰＡＧＥ）分离,然后进行电泳图谱及信息收集。应用ＧｅｎｅｓｃａｎＴＭ ３．０ 软件和Ｇｅｎｏ－ｔｙｐｅＴＭ ２．１ 软件进行基因分型和基因定位。　结果　在３５ 个家系中共有１９３ 个微卫星标志能准确进行基因分型。共得４１ ４９５ 个基因型。经过多点连锁分析和患病同胞对分析,初步确定在１,１０,１２,１８,２０号染色体上存在ＮＩＤＤＭ 相关基因位点。　结论　用全基因组扫描技术可以对中国人２ 型糖尿病相关基因位点进行基因分型和基因定位。     

一个精神发育迟滞高发村的流行病学调查

对湘西某精神发育迟滞高发村进行流行病学调查,使用 Logistic 回归方法分析危险因素。结果表明该村精神发育迟滞的总患病率为28.93%。当地智力普遍偏低系多因素所致,除环境缺碘外,脑部疾病是该村中、重度精神发育迟滞的主要危险因素,患者受教育程度与轻度精神发育迟滞的发生明显相关,当地落后的社会文化因素亦不容忽视,提示在缺碘地区采取综合性措施治理精神发育迟滞的必要性。     

Long-term echocardiographic follow-up after posterior mitral annuloplasty using a vascular strip for ischemic mitral regurgitation: ten-years of experience at a single center

Management of ischemic mitral regurgitation (MR) is challenging. The aim of this study was to investigate long-term clinical and echocardiographic results of restrictive mitral annuloplasty for ischemic MR. From 2001 through 2010, 96 patients who underwent myocardial revascularization with restrictive mitral annuloplasty using a vascular strip for ischemic MR were analyzed. Patients were stratified into two groups based on left ventricular ejection fraction (LVEF): group I, n = 50, with LVEF > 35% and group II, n = 46, with LVEF ≤ 35%. The early mortality rate was 2.1% (2/96) and the late cardiac mortality rate was 11.5% (11/96). MR grade was reduced at discharge (0.8 ± 0.7) but increased during follow-up (1.1 ± 0.8, P = 0.001). There was no intergroup difference in terms of freedom from recurrent MR ≥ moderate eight years after surgery (94.1% ± 5.7%, group I vs 87.8% ± 7.2%, group II; P = 0.575). NYHA functional class (odds ratio [OR], 2.2; P = 0.044) and early postoperative residual MR ≥ mild (OR, 25.4; P < 0.001) were independent predictors of recurrent MR. Restrictive mitral annuloplasty using a vascular strip is effective in ischemic MR. It is important to avoid early postoperative residual MR.     

全国儿童智力低下的现患率研究

本研究的目的是了解我国儿童智力低下的现患率及其分布特征。采用分层、不等比例、多阶段、随机整群的抽样方法和智力筛查和诊断方法。我国儿童智力低下总现患率为１．２７％，城市为０．７７％，农村为１．４１％，男性高于女性，现患率随年龄增长而增高。     

Sperm segregation analysis of a (13;22) Robertsonian translocation carrier by FISH: a comparison of locus-specific probe and whole chromosome painting

BACKGROUND: The t(13;22) Robertsonian translocation constitutes a rare form of rearrangement between acrocentric human chromosomes. Most of the meiotic segregation studies of human Robertsonian translocations have been performed on common t(13;14) and t(14;21) translocations. Analysis of the chromosomal constitution in sperm of Robertsonian translocation carriers is of great interest for assessing the risk of unbalanced forms and adapting genetic counselling. In the present study, we present the first meiotic segregation study of a t(13;22) Robertsonian translocation in human sperm. METHODS: A total of 11 787 sperm nuclei were scored using two distinct FISH labelling techniques, i.e. the locus-specific probes (LSI) method and the whole chromosome painting (WCP) technique. RESULTS: The frequency of normal or balanced sperm resulting from alternate meiotic segregation was 86%. Incidences of unbalanced complements resulting from adjacent segregation modes were 12.79% and 14.36% in LSI and WCP assays, respectively. No significant excess of nullisomy or disomy for the affected chromosomes was observed. CONCLUSIONS: Similar results in segregation were obtained with the two techniques, demonstrating the efficiency of the two strategies for the direct segregation analysis of Roberstsonian translocations. The results obtained indicated a moderate meiotic production of imbalance. This study shows that the rare Robertsonian translocation (13;22) displays a similar distribution of balanced and unbalanced sperm patterns as the common Robertsonian translocations previously studied. This suggests that the behaviour of acrocentric chromosomes was similar in all cases of centric fusion.     

双源螺旋CT对非缺血性二尖瓣反流机制的研究

目的运用双源螺旋CT（DSCT）探寻非缺血性二尖瓣反流的反流机制。方法超声诊断为二尖瓣反流并行CT俭查的46例患者．其中男性28例,女性18例;年龄37～81岁,平均年龄63．57岁。二尖瓣反流组依据多普勒超声检查分为轻度反流组（20例）、中度反流组（14例）、重度反流组（12例）。分别在cT图像上测量收缩中期幕状面积、幕状高度、二尖瓣瓣环前后径、联合间距离等二尖瓣装置形态参数。另随机选择无二尖瓣反流的体检者43例作为止常埘照组．．结果小同程度二尖瓣反流组在幕状面积、幕状高度、瓣环前后径、收缩中期和舒张末期瓣环面积较正常对照组差异有统计学意义（P〈O．05）。而瓣环联合间径差异无统计学意义（P〉0．05）。不同程度二尖瓣反流组在舒张期左心室短轴长度、球形度．收缩期左心室长径、舒张末期容积（EDV）、收缩末期容积（ESV）差异有统计学意义（P〈0．05）,、乳头肌间距变化度、左心事长径位移度组间差异均无统计学意义（P〉0．05）。结论DSCT功能检查对二尖瓣反流机制研究有重要价值,、非缺血性二尖瓣反流乃因心室-瓣膜环受过重前负荷而扩张．导致前外侧乳头肌腱索对前叶体部的过度牵拉．致使精确闭合的双侧瓣叶产毕前叶的云云h不对称导计对合而稠的减少,产生反流。     

Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy

A total of 162 Duchenne (DMD) patients and two girls with a DMD phenotype were analysed for deletions in the central region of the dystrophin gene in order to determine if there was a correlation between mental retardation (MR) and the pattern of deletion. Approximately 43% of the patients studied had deletions with two dystrophin cDNAs, cf23a and cf56a, and among 148 patients who were mentally assessed, 50% were mentally retarded. The average IQ in the group of patients with DNA deletions did not differ significantly from those patients with no detectable deletions. However, six unrelated DMD boys with MR showed an identical pattern of deletion. Our observations in the group of patients who had detected DNA deletions suggest that exon 52 of the dystrophin gene may be functionally significant in the manifestation of MR: 70% (19/27) of patients with a deletion of this exon were mentally retarded, whereas only 38% (15/39) of MR patients had deletions not involving exon 52. This difference was statistically significant.     

2项必选数字记忆测验在精神发育迟滞鉴定中的对比研究

目的探讨2项必选数字记忆测验得分在精神发育迟滞患者司法鉴定与非鉴定组的异同。方法精神发育迟滞（MR）患者司法精神医学鉴定者43例,非鉴定者44例,分别进行2项必选数字记忆测验（BFDMT）和韦氏成人智力量表测查（WAIS-RC）,对鉴定组和非鉴定组之间的结果进行比较和分析。结果MR鉴定组总分、容易条目得分明显低于非鉴定组（分别为P〈0.05、P〈0.001）,在困难条目得分上两组之间无显著性差异（P〉0.05）;鉴定组的智商、言语智商值都明显低于非鉴定组,有显著性差异（P〈0.05）;操作智商两组之间无显著性差异（P〉0.05）。MR鉴定组BFDMT测验总分、容易条目分、困难条目分与WAIS-RC测验的智商总分、言语智商、操作智商分之间均呈显著正相关。结论BFDMT得分的高低有助于司法鉴定MR患者的诊断。     

The ARX mutations: a frequent cause of X-linked mental retardation

The ARX gene mutations have been demonstrated to cause different forms of mental retardation (MR). Beside FMR1, in families with X-linked mental retardation (XLMR), the ARX dysfunction was demonstrated to be among the most frequent causes of this heterogeneous group of disorders. Nevertheless, in sporadic cases of MR, ARX mutations are extremely rare. In order to evaluate the frequency of ARX mutation in XLMR, we performed mutational analysis of ARX in 165 mentally retarded probands negative for FRAXA and belonging to families in which the condition segregates as an X-linked condition. The same recurrent mutation, an in frame 24 bp insertion (c.428-451 dup (24 bp)), was identified in five patients. In one family, the mother of two affected boys was found not to carry the mutation detected in her sons. These data suggest the presence of germline mosaicism for the mutation in the mother. Our results confirm the significant contribution of ARX mutations in the etiology of MR, especially in this group of patients selected for XLMR (3%). These data, together with those reported in the literature, imply that screening for c.428-451 dup (24 bp) mutation should be recommended in all patients with suspected XLMR.     

1680例智力低下儿童的遗传咨询研究

1991年10月至1997年6月通过遗传咨询观察了智力低下（MR）儿童1680例,其中男性占53．3％,女性占46．7％;伴癫痫者占11．2％,伴脑瘫者占21％,第一胎占82．6％,轻度MR占73．8％,中度MR占22．9％,重度MR占3．3％,染色体核型异常检出率为14．6％．其中常染色体异常占73．1％,性染色体异常占26．9％,在病因探讨中,属于出生前因素占41．2％．出生时因素占26．5％,出生后因素占2．7％,原因不明占29．6％。     

Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience

Objective: The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre.

Methods: Inclusion criteria were: age <18 years at referral, IQ<85, no aetiological diagnosis after complete examination, which included karyotyping with high resolution banding (HRB).

Results: In 266 karyotyped children, anomalies were detected in 20 (7.5%, seven numerical, 13 structural); 39 cases were analysed by FISH for specific interstitial microdeletions, and anomalies were found in nine (23%). FISH analyses for subtelomeric microdeletions were performed in 184 children (44% moderate-profound MR, 51% familial MR), and one rearrangement (0.5%) was identified in a non-familial MR female with mild MR (de novo deletion 12q24.33-qter). The number of probable polymorphisms was considerable: 2qter (n=7), Xpter (n=3), and Ypter (n=1). A significantly higher total number of malformations and minor anomalies was present in the cytogenetic anomaly group compared to the group without cytogenetic anomalies.

Conclusions: The total frequency of cytogenetic anomalies in this prospective study was high (1:10), but the frequency of subtelomeric rearrangements was low. The most likely explanations are the high quality of HRB cytogenetic studies and the lack of clinical selection bias. Conventional cytogenetic analyses, combined with targeted microdeletion testing, remain the single most effective way of additional investigation in mentally retarded children, also in a tertiary centre.