家族性高胆固醇血症家系低密度脂蛋白受体基因突变分析

家族性高胆固醇血症(FH)是一种严重的常染色体单基因显性遗传性疾病,临床特点为血浆胆固醇大幅增高、特征性黄色瘤和早发冠心病,同时具有阳性家族史。低密度脂蛋白受体(LDLR)基因突变是引起FH最主要的原因。本研究对一临床诊断为纯合子FH先证者及其父母进行基因突变分析,以从分     

家族性高胆固醇血症的临床与基因治疗新进展

家族性高胆固醇血症（FH）是一种常染色体显性遗传病，临床表现为血浆总胆固醇和低密度脂蛋白胆固醇水平升高、皮肤或肌腱黄色瘤和早发冠心病。FH的治疗手段主要包括临床治疗和基因治疗，近年来新药的研发和基因研究的快速发展为FH的治疗提供了更多的手段，本文将对FH的临床和基因治疗的新进展进行综述。     

家族性高胆固醇血症姐妹二人基因突变分析

家族性高胆固醇血症（familial hypercholesterolemia，FH）是一种较为常见的常染色体显性遗传病，其主要特点为血浆胆固醇水平极度增高，多部位皮肤肌腱黄色瘤和过早发生冠心病，严重者青少年时期发生心肌梗死甚至死亡。本研究对临床确诊为纯合型家族性高胆固醇血症两姐妹进行聚合酶链反应—单链构象多态性（PCR—SSCP）结合银染技术、     

家族性高胆固醇血症一家系调查

目的：了解家族性高胆固醇血症的临床及遗传特征。方法：对家族性高胆固醇血症一家系４５名家族直系成员进行了调查，检查了所有成员血清总胆固醇（ＴＣ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）及甘油三酯（ＴＧ）。结果：发现其中有１２例患家族性高胆固醇血症，患病率为男３２％（８／２５），女２０％（４／２０），总患病率为２６．７％。遗传方式符合常染色体显性遗传。临床特征为：①血清ＴＣ、ＬＤＬ－Ｃ自儿童期即增高，且随年龄的增长有逐渐增高的趋势，ＴＧ正常或稍高；②自３５岁后逐渐出现黄色瘤、运动试验阳性，４０岁后出现脂性角膜弓及心绞痛且逐渐加剧，５０岁后可出现心肌梗死甚至猝死。结论：家族性高胆固醇血症是一种常染色体显性遗传性疾病，血清ＴＣ、ＬＤＬ－Ｃ升高及黄色瘤、脂性角膜弓、早发冠状动脉粥样硬化性心脏病（冠心病）是其临床特征     

胃黄色瘤与萎缩性胃炎相关性的单中心回顾性研究

背景:胃黄色瘤是一种少见的胃部良性病变,确切病因不明。研究发现胃黄色瘤患者多合并萎缩性胃炎。目的:探讨胃黄色瘤与萎缩性胃炎的相关性及其临床意义。方法:连续纳入2015年4月—2016年3月在山西省人民医院行胃镜检查的10 645例患者,采集人口统计学、临床、内镜、组织学相关信息进行回顾性分析。结果:入组患者胃黄色瘤检出率为2.9%。胃黄色瘤患者的平均年龄和萎缩性胃炎检出率(47.9%对16.6%)显著高于非胃黄色瘤患者,且胃黄色瘤患者胃黏膜萎缩程度更为严重(P均0.001);多因素Logistic回归分析显示年龄≥50岁(校正OR=1.349,95%CI:1.042~1.747,P=0.023)和萎缩性胃炎(校正OR=3.892,95%CI:3.076~4.924,P0.001)是胃黄色瘤的独立危险因素。萎缩性胃炎患者的胃黄色瘤检出率亦显著高于非萎缩性胃炎患者(7.9%对1.8%,P0.001)。对性别、年龄匹配的胃黄色瘤与非胃黄色瘤患者的分析表明胃黄色瘤独立于性别、年龄而与萎缩性胃炎相关(P0.001)。此外,胃黄色瘤患者中,合并萎缩性胃炎者的多发性胃黄色瘤检出率显著高于未合并萎缩性胃炎者(32.0%对13.8%,P0.001)。结论:胃黄色瘤的发生与患者年龄以及萎缩性胃炎及其严重程度有关。萎缩性胃炎可能是胃黄色瘤的病因之一,而胃黄色瘤可能是萎缩性胃炎胃黏膜病变的另一种表现形式。     

眼睑黄色瘤1104例患者血脂7项的调查分析

目的 对1 104例眼睑黄色瘤患者的血脂7项进行调查与研究。方法 采用整群抽取的方法,对被调查者进行眼睑黄色瘤筛查和空腹血清三酰甘油(triacylglycerol,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein-cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C),载脂蛋白-A1(apolipoprotein-A1,Apo-Al),载脂蛋白-B(apolipoprotein-B,Apo-B),脂蛋白(a)[lipoprotein(a),Lp(a)]检测。结果 眼睑黄色瘤发病率为2.58%(1 104/42 691),女性(3.09%)高于男性(2.04%),差异有统计学意义(χ²=46.82,P<0.01)。血脂异常发病率为39.76%(16 972/42 691),男性(45.59%)高于女性(34.35%),差异有统计学意义(χ²=562.29,P<0....     

家族性高胆固醇血症临床表型及其与基因型关系

正家族性高胆固醇血症(familial hypercholesterolemia,FH)是一种以血浆总胆固醇(total cholesterol,TC)和低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平增高,身体不同部位的皮肤或肌腱散发大小不等的黄色瘤及早发冠心病(premature coronary artery disease,PCAD)为     

家族性高胆固醇血症1例

患儿,男,14岁,1993年5岁时发现皮肤黄色瘤,1997年到我院就诊,无胸闷及体力活动受限,双肺呼吸音清晰,心率78次/min,心尖部及主动脉瓣听诊区可闻及Ⅱ级收缩期吹风样杂音,双颈部可闻及Ⅲ级收缩期吹风样杂音,肘、膝关节伸侧,手背及跟腱处多发性黄豆至花生米大小黄色瘤。血、尿常规,肝肾功能,血糖及心电图均正常,3次查血浆总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)均显     

胃黄色瘤与胃癌及其癌前病变相关性的研究进展

胃黄色瘤又称胃黄斑瘤或胃脂质岛,是一种发生于胃黏膜的脂肪沉积型良性病变。其病因和发病机制尚不完全明确,可能与胃黏膜损伤修复、肠化生、脂质代谢异常有关。胃黄色瘤可发生于胃任何部位,常见于胃窦和幽门区。据报道,胃黄色瘤与早期胃癌风险增加相关。本文就胃黄色瘤与胃癌及其癌前病变相关性的研究进展作一综述。     

家族性高胆固醇血症双基因突变相关性研究进展

家族性高胆固醇血症(FH)是一种常染色体(共)显性遗传的脂蛋白代谢紊乱性疾病[1],主要临床表现为:低密度脂蛋白胆固醇(LDL-C)水平不同程度升高、皮肤和(或)肌腱黄色瘤、脂性角膜弓、早发冠状动脉粥样硬化性心脏病(pCHD)[2,3].临床上将FH分为纯合子型家族性高胆固醇血症(HoFH)和杂合子型家族性高胆固醇血症...     

A Pedigree Analysis of a Family With Familial Hypercholesterolemia

Objective The current study was designed to investigate the features of a family with familial hypercholesterolemia(FH). Methods Twenty members of three generations in a family with FH were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. Results The proband was a 41 years old male who suffered from angina pectoris with multi-vessel stenosis of coronary artery at the age of 40. Among 20 members, 8 individuals were demonstrated with hypercholes-terolemia in this family with the total incidence of 40% [54.5% (6/11) in male and 22. 2% (2/9) in female The serum total cholesterol level was elevated in childhood from 7. 1 to 10. 8 mmol/L and tended to be raised with increasing age. In addition, the level of total cholesterol was found to be elevated both in a monozy-gote twin brothers and their offspring in the family. Conclusion FH appears to be a hereditary disease of autosomal dominance inheritance and the outcome of FH patients with coronary hea     

A pedigree analysis of familial hypercholesterolemia in monozygote twin brothers

The current study was designed to investigate the features of a family with familial hypercholesterolemia (FH). Twenty members of 3 generations in a family with hypercholesterolemia were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. The proband was a 41-year-old male who suffered from angina pectoris with multi-vessel stenosis of coronary arteries at the age of 40. Among 20 members, 8 individuals had FH in this family with a total incidence of 40% (54.5% [6/11] in male and 22.2% [2/9] in female). The serum total cholesterol level was increased in childhood from 7.1 to 10.8 mmol/L and tended to increase with increasing age. In addition, the level of total cholesterol was increased in monozygote twin brothers and their offspring in the family. This pedigree analysis showed that FH appears to be a hereditary disease of autosomal dominance, and attention should be paid, especially in the only son or daughter society of China.     

低密度脂蛋白受体功能与基因突变的关系

目的：分析家族性高胆固醇血症低密度脂蛋白受体（LDLR）功能变化,寻找基因突变位点;阐明该基因突变类型对LDLR功能的影响。方法：患儿及其你系、母系三代共30人检查血脂和临床表现,作系谱分析,确定该患儿符合家族性高胆固醇血症纯合子的诊断;培养患儿皮肤成纤维细胞,用受体的放射性配体结合技术,定量测定细胞的LDLR的功能;提取外周血基因组DNA对LDLR基因的相应外显子进行PCR－SSCP及DNA序列分析。结果：系谱分析发现11个杂合子及1个纯合子;纯合子患儿LDLR结合功能基本正常,但其内移和降解功能只有正常人的3．6％及1．7％;DNA测序结果证实患儿第17外显子的第599和600密码子间插入一个碱基G,导致框移突变;第842密码子发生CCA→CCG的无义突变。结论：首次报道了一个新的LDLR突变位点;初步明确该突变位点对患者的影响较为显著。     

Familial hyperamylasaemia.

A six year old boy underwent extensive investigation for recurrent abdominal pain and was found to have a persistently raised serum amylase. Endoscopic retrograde cholangiopancreatography was normal and macroamylasaemia was excluded. Serum amylase concentrations were found to be raised in other family members spanning three generations, all of whom were asymptomatic. Clearance studies suggested no evidence of a renal tubular defect and serum lipase concentrations were normal. This is the first report of apparently familial hyperamylasaemia and the mode of inheritance is consistent with an autosomal dominant pattern.     

家族性高胆固醇血症一家系分析

目的高胆固血脂一家系调查。调查一家族性高胆固醇血症（FH）三代共20名成员，其中包括一对孪生兄弟的患病情况。结果提示HF患者共8例。总患病率为40％，男性患病率为54．5％（6／11），女性患病率为22．2％（2／9），符合常染色体显性遗传。结论本例FH的家系特点为：①血清总胆固醇（TC）从儿重期始有增高，且随年龄的增长有增高趋势；②家系中一对单卵双生的孪生同胞均为患病者，其后代亦有TC增高；③先证者41岁起即以典型的卧位型心绞痛起病，冠状动脉造影提示三支冠状动脉多处严重狭窄，似提示FH家系中的冠心病患者发病早且病变严重。     

姐妹2人同患家族性高胆固醇血症家系LDL-R基因突变分析

目的:对临床确诊的家族性高胆固醇血症(FH)两姐妹及其家系成员进行低密度脂蛋白受体(LDL-R)基因突变分析,探讨其发病机制。方法:提取患者外周血基因组DNA,聚合酶链反应分别扩增启动子和18个外显子片断,采用单链构象多态性(PCR-SSCP)结合银染技术,对异常电泳条带进行核苷酸序列分析。结果:姐妹2人及其父亲,叔叔,祖母均发现LDL-R基因第13外显子存在一个错义突变,与GeneBank对照证实第1879位G→A碱基置换,氨基酸的改变为丙氨酸→苏氨酸(A606T突变),其母亲和女儿经测序并未发现此突变位点。结论:姐妹2人均为LDL-R基因存在A606T杂合错义突变,并均来自其父系亲属;可能是该家系发病的分子基础。     

一个新的肝细胞核因子1α仪基因突变致青少年的成人起病型糖尿病3型家系报道

目的探讨一个青少年的成人起病型糖尿病（MODY）家系的致病基因。方法对一例发病9年的32岁女性糖尿病患者家系成员进行调查,该家系中有两代糖尿病患者,采用目标区域捕获高深度测序技术在先证者中找到突变基因,使用Sanger测序技术验证突变位点并筛查其他家系成员。结果基因检测发现家系中3个个体携带肝细胞核因子1仅（HNF·1α）基因V380Cfs。39移码突变,该突变在家系中表现为与糖尿病共分离。结论该家系为一个新的HNF-1α仅基因突变所致MODY3家系。     

一个遗传性血色病家系的临床特点及其遗传基础初探

目的 探讨一个遗传性血色病家系的临床特点及初步查找该家系的遗传基础. 方法对该家系成员进行问诊、体检、实验室检查、多器官MRI检查、肝穿刺活组织检查(铁染色),绘制家系图谱.采集血样,对常见的遗传性血色病致病基因进行测序分析. 结果该家系成员中有7人存在铁过载,临床诊断为遗传性血色病.家系患者代代相传,无性别差异,外显率约46%.常见的SLC40A1和HFE基因突变位点在该家系成员中未发现. 结论该遗传性血色病家系患者以皮肤色素沉着、肝脾等脏器铁沉积最具特征,为常染色体显性遗传,但其遗传基础尚不明确.     

Hereditary pheochromocytoma--a family affected by von Hippel-Lindau disease

The authors present a case of a 37 year old male (proband) with a 13 year history of progressive sight impairment leading to blindness and a 4 year history of a mild hypertension. He was incidentally found to have large adrenal tumors after an ultrasound kidney examination. The tumors were confirmed with CT scan and magnetic resonance imaging. A bilateral pheochromocytoma was biochemically demonstrated and successfully removed. The eye diagnosis of angiomatosis retinae von Hippel-Lindau was ascertained after a search of the patient files in other medical departments, which led to a family screening. Proband's brother, having hypertension and a history of a cerebellar astrocytoma operation, was also diagnosed with CT scan to have a bilateral pheochromocytoma. Unfortunately, at the same time he was found to have a large irremovable neuroendocrine pancreatic carcinoma, which caused complications and his eventual death. Both proband and his brother were affected by the same CGG(Arg167)->CAG(Gln) mutation in the exon 3 of the VHL gene. Other living and examined family members were not affected, which was confirmed by negative genetic testing. One year after the pheochromocytoma operation, proband was diagnosed to have a retroperitoneal tumor left to the aorta, clinically silent, with slightly and non-constantly elevated urine norepinephrine and normetanephrine. Metaiodobenzylguanidine scintigraphy showed that it was a paraganglioma. The old CT and magnetic resonance picture review demonstrated that the tumor had already been present at the time of the operation. It was surgically removed and histologically verified. It is a pity that proband had not been sent by his ophthalmologist for an endocrine examination when the eye diagnosis was determined. Affection of the family would have been discovered earlier, and proband's brother might have possibly been saved.     

AV nodal reentrant tachycardia with a bystander Mahaim fiber

A 13 year old boy had a wide QRS complex tachycardia. A discontinuity in the AV nodal functional curve was observed in the electrophysiologic study. The AV internal was prolonged in association with progressive ventricular preexcitation. At maximal preexcitation, the HV interval was -20 msec and the QRS complex was identical to that seen during clinical tachycardia. No VA conduction was found and atrial premature beats did not affect the tachycardia. The His deflection was found at variable timing when tachycardia was induced. These findings confirmed that tachycardia originated within the AV node and was conducted to the ventricle over the Mahaim fiber. The short effective period of the Mahaim fiber had clinical significance since when atrial fibrillation developed, a rapid ventricular response was observed.