远端型肌营养不良症系谱调查与分析

肌营养不良症（MuscularDystrophies）是一组原发于肌肉的遗传性变性疾病，属常染色体显性遗传。主要临床特征为受累骨胳肌的进行性萎缩、无力。远端型肌营养不良症（Gower型）最为少见，病因尚不清楚。1临床资料患者女性，48岁。40岁开始手部肌肉萎缩，以大鱼际肌萎缩明显，并有握拳无力，逐渐发展到下肢肌肉萎缩，行走无力；感觉无异常，健反射低下。47岁就治于各大医院，血清磷酸肌酸激酶活性（CPK）Hughes比色法4OU％，EMG呈肌病型，肌肉活检：酸性磷酸酶染色阳性的空泡变性。尽管进行治疗，无明显好转。2系谱调查及结果远端型肌营…     

遗传性脊髓型Friedreich和脊髓小脑型共济失调的临床及系谱分析

报告脊髓型Ｆｒｉｅｄｒｅｉｃｈ共济失调的三个系谱和脊髓小脑共济失调系谱。结果：前者起病年龄较小，后者起病年龄较大，两种类型的共济失调的症状繁多，交叉重叠、不易区分、进行系谱分析，有助于正确诊断，对分型有一定帮助。     

多发性神经纤维瘤病一家系分析

病例与家系1.病例:患者,女,68岁,出生时身上发现多数褐色斑疹,25岁开始胸部、背部出现数个黄豆大小圆形软肿物,并缓慢增多,波及全身。2011年3月因"黑便、头晕、乏力"收入我院,查体:神清言明,发育正常。贫血貌,周身皮肤满布大小不等的坠生物,质软,咖啡色,皮肤弹性减退;心肺听诊无异     

2型糖尿病家系发病特征与危险因素初步调查

Objective To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. Methods A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM) , maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. Results No gender difference was found in the prevalence of T2DM (42. 59% in male and 48. 18% in female respectively, P ＞0. 05) , nor was the newly diagnosed rate(9. 89% in male and 11. 82%in female, P ＞ 0. 05). The onset age was (63. 3 ± 12. 4) years old in the first generation [(64. 4 ± 12. 5)years in male and (62. 3 ± 10. 3) years in female] , (47. 1 ± 8. 7) years old in the second generation [(48. 2 ±9. 3)years in male and (46. 1 ± 8. 1) years in female] , (29. 6 ± 10. 2) years old in the third generation [(28. 9 ±9. 5)years in male and (30. 0 ± 10. 4)years in female]. Compared with normal glucose tolerance (NGT) subjects , newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM[(68. 4 ±12. 4)kg, (69. 5 ± 11. 0)kg and (69. 1 ±9. 6)kg] and IGR[(66. 1 ±10.7)kg, (65.9 ± 10.7) kg and(65.7 ± 10.4) kg] , when compared with NGT [(61.0 ± 10.2) kg,(59. 5 ±11.0) kg and (60. 1 ± 10. 4) kg, all P ＜ 0. 05] . The same results were obtained with waist circumference and waist-hip ratio [(4. 1 ± 12. 5) cm and 0. 92 ± 0. 36 in newly diagnosed T2DM while (89. 1 ± 10. 7) cm and 0. 90 ± 0. 64 in IGR] , when compared with NGT[(82. 5 ± 10. 1) cm and 0. 82 ±0. 25] , all P ＜0. 05. Conclusions No gender difference was found in the onset characteristics of T2DM.High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.     

Mutation analysis of type Ⅱ hair keratin gene in a pedigree with monilethrix

Objective To investigate the mutation of type Ⅱ human hair basic keratin (hHb) gene in a family with monilethrix.Methods Scanning electron microscopy was used to observe the structure of hair shafts.With informed consent,blood samples were drawn from affected and unaffected membets in this family,as well as from 50 healthy controls.Genomic DNA was isolated from these samples.The exon 1 and exon 7 of hHb1,hHb3 and hHb6 were amplified by polymerase chain reaction (PCR).All the PCR products were sequenced directly using ABI3730 automated sequencer.DNA sequence alignment was carried out with BLAST software.Results A typical beaded appearance was observed in affected hairs by using scanning electron microscopy.There were obvious longitudinal ridges and sulcuses in hair node.and hair cuticles were irregularly shaped.Most cortex and medullary substance were absent in affected hairs of a patient.After sequence alignment,a G1289A point mutation in exon 7 of hHb6 gene,which led to a substitution of arginine for glutamide at codon 430,was detected in affected members of this family,but not in unaffected family members or 50 unrelated human controls.No mutation was observed in exon 1 or exon 7 of hHb1 and hHb3 gene or exon 1 of hHb6 gene.Conclusion The missense mutation of R430Q is a novel mutation.which may be associated with the pathogenesis of monilethrix in this pedigree.     

一个类孟买家系的分子遗传学分析

目的探讨一个类孟买家系的分子遗传学机制。方法采用血清学方法鉴定先证者及其父母的红细胞H抗原。采用高保真PCR扩增先证者及其父母的α1,2岩藻糖基转移酶(FUT1)基因编码区序列。PCR产物经TA克隆后进行测序、比对分析FUT1基因编码区序列。结果凝胶电泳分析证实成功扩增FUT1基因编码区序列;克隆后测序、比对分析发现先证者检出1种已知突变(h1nt547-552△AG),为h1/h1纯合子;先证者父母为H/h1杂合子。结论 FUT1基因突变以常染色体隐性遗传方式导致先证者类孟买血型的形成。     

CRYGD基因突变与一中国先天性核性白内障家系致病相关

目的对一先天性核性白内障家系进行候选致病基因的筛查,以明确其发病分子基础。方法以家系先证者基因组DNA为模板,聚合酶链反应(PCR)扩增10个白内障候选致病基因的突变热点区域,PCR产物纯化后进行直接DNA测序筛查突变位点。如发现疑似突变位点,则利用直接DNA测序法对该突变位点在家系其他成员的存在情况进行疾病表型与致病突变共分离分析,进一步确认其是否为致病性突变位点。结果该家系三代呈常染色体显性遗传,临床表型大致相同,可确诊为先天性核性白内障。候选致病基因筛查发现在患者的CRYGD基因外显子2发现一个杂合突变c.C70A,正常家系成员无此突变,临床表型与基因型共分离。该突变为错义突变,导致一个CRYGD蛋白第24位的脯氨酸被苏氨酸取代(p.P24T)。结论 CRYGD(p.P24T)突变是导致该先天性核性白内障家系的致病分子基础。     

母亲与婴儿亚甲基四氢叶酸还原酶C677T多态性与早产和低出生体重的相关性研究

目的:探讨早产和低出生体重与母亲和婴儿5-10亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态性的关系.方法:采用病例对照及核心家系的研究设计,共调查了500个核心家系,包括250个正常孕周出生的核心家系和250个早产核心家系.采用盐沉淀法提取基因组DNA,通过聚合酶链式反应(PCR)对5-10亚甲基四氢叶酸还原酶基因C677T多态性进行基因型鉴定.通过SAS软件的广义线性模型(GENMOD),选用对数线性模型(Log-linear Model)中的泊松回归进行最大拟然比检验(Maximum Likelihood Ratio Test),分析母亲和婴儿MTHFR基因分别与早产和低出生体重的关系.结果:首先,我们采用TDT方法分别检验了早产和低出生体重对照核心家系MTHFR 677T等位基因传递是否平衡,研究结果表明MTHFR 677T突变等位基因传递符合孟德尔遗传规律.之后,我们分析了MTHFR基因与早产和低出生体重的关系.结果显示:婴儿MTHFR CT 和TT基因型不但增加早产的发生危险性且具有显著的统计学意义(CT基因型:OR＝2.01,95%CI为1.21～3.32;TT基因型:OR为1.82,95%CI为1.02～3.26),而且婴儿MTHFR基因能够增加低出生体重的发生危险且具有显著的统计学意义(CT基因型:OR＝1.87,95%CI为1.08～3.24;TT基因型:OR＝1.90,95%CI为1.02～3.54).但是母亲MTHFR基因对早产和低出生体重的影响均没有显著的统计学意义.我们进一步观察了母亲与婴儿MTHER基因之间的交互作用对早产和低出生体重的影响,研究结果表明母亲与婴儿MTHFR基因之间无明显交互作用存在.结论:婴儿MTHFR基因CT和TT基因型能够增加早产和低出生体重发生风险且有显著的统计学意义,在早产核心家系中MTHFR677T突变等位基因不符合孟德尔遗传规律,可能是导致早产的遗传易感位点,并且MTHFR 基因有可能通过孕周的缩短(早产)而导致低出生体重这一生殖结局的发生.     

4个常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病(CADASIL)家族的临床表现

目的:报道我国4个常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病(CADASIL)家族的临床特点.方法:收集4个通过病理和基因检查确诊为CADASIL的先证者及其家族成员的临床资料,对4个先证者做心电图检查,2个先证者进行周围神经电生理检查.结果:4个家族共调查83个家庭成员,总共29人出现神经系统损害的临床症状.每个家族中连续数代均有发病者,男女均受累及,符合常染色体显性遗传特点,所有患者均无常见的脑血管病的危险因素,发病年龄为28～70岁,以40～50岁为主.主要临床表现为发作性头晕、轻偏瘫,发病同时或短期内出现智能下降.所有患者均无偏头痛发作.1个先证者出现手套和袜套样痛觉减退,2个先证者周围神经电生理检查结果异常.所有先证者心电图检查均未见异常改变.结论:我国CADASIL患者早期可以主要表现为椎-基底动脉系统缺血的症状,智能下降可以在疾病早期发生,偏头痛可能不是我国患者的主要表现.本病可出现周围神经的损害.