044 X-连锁腓骨肌萎缩症:QJB1(连结32)基因127位点异常突变

X-连锁显性腓骨肌萎缩症（CMTX1）是一种遗传性神经病，CMTX1起初是轴突病变还是脱髓鞘病变至今还未明了。本文报道1例CMTX1家庭首先影响髓鞘然后导致轴突变性的病例。     

遗传性肩胛腓骨肌萎缩症一个家系分析

运动神经元病（MND）的脊肌萎缩症（SMA）分为6个类型,肩胛腓骨型很少见,其中遗传性肩胛腓骨肌萎缩症（SPSMA）国内报道较少,我们报道一个SPSMA 家族,并对其临床表现、电生理、肌酸磷酸激酶（CK）、肌肉病理等特点进行了讨论.     

腓骨肌萎缩症一家系的临床特征与突变基因分析

目的 分析腓骨肌萎缩症(CMT)一家系的临床特征与突变基因.方法 回顾性分析1例CMT患者的临床特征并对其一级亲属进行家系调查.采用多重连接依赖式探针扩增技术分析该家系成员的突变基因,然后进行一代DNA测序验证.结果 本例CMT患者青年发病,临床特征主要为缓慢进行性四肢远端肌无力伴肌萎缩,同时出现腱反射降低或消失;脑脊...     

1例儿童Charcot-Marie-Tooth病INF2基因突变诊断及治疗分析

目的 分析1例Charcot-Marie-Tooth病（CMT）患儿的病例资料和INF2基因突变情况,总结该病的诊治经验。方法 对1例因双侧足部畸形就诊于的患儿进行临床及实验室检查,通过全外显子组测序进行测序分析,并对其父母进行Sanger测序验证。结果 男性患儿,10岁,双足内收内翻畸形,双下肢腓骨肌萎缩无力,肌电图提示多发性神经受损。基因检测显示,定位于14号染色体上的INF2基因存在1处杂合突变,c206T>C(p. L69P),该杂合突变Sanger测序的家系验证结果显示为新生突变,父母均无该位点突变。文献检索发现,该患儿临床表型与国外已报道的病例相似,但该患儿目前尚无肾脏受累表现;国内尚无报道。行右足跟腱延长+胫后肌、腓骨长肌、胫前肌三腱编织合一+跖腱膜切断手术治疗,术后足部外观恢复较好,仍在随诊观察中。结论 该例患儿INF2基因杂合突变导致CMT病,临床表现为腓骨肌萎缩无力和足部畸形;CMT的诊断需结合病史、临床表现和体征、有无相关家族史、神经电生理和病理学检查以及分子遗传学检测做出综合判断;足部畸形可采用手术矫形治疗。     

青年缺血性卒中患者的基因突变

缺血性卒中是一种多基因遗传性疾病，并由多种危险冈素叠加而致发病．其发病率和致残率均较高。遗传因素对于青年人缺血性卒中的影响作用较大?文章对与青年人缺血性卒中有关的血小板相关基因、凝血／纤溶基因、脂代谢基因、同型半胱氦酸代谢基因等作了综述。     

脊肌萎缩症的分子遗传学研究进展

脊肌萎缩症(SMA)是一组常见的常染色体隐性遗传病，居致死性常染色体隐性遗传病的第二位。近年来，在SMA的分子遗传学研究方面取得了重大进展，其发病可能与运动神经元存活基因、神经元凋亡抑制蛋白基因和P44基因的突变有关。     

脊髓性肌萎缩症表型及相关基因的研究进展

脊髓性肌萎缩症(SMA)是常见的神经肌肉系统常染色体隐性遗传病,运动神经元存活基因1(SMN1)为其致病基因.目前多项研究表明该病为多系统受累疾病,除了神经肌肉系统外,还包括心血管系统、消化系统、代谢系统、泌尿生殖系统等.患者临床表现多样、致病突变相同表明其存在遗传及环境修饰因子等因素影响,如运动神经元存活基因2拷贝数...     

脊髓性肌萎缩症患者神经元样细胞SMN2基因mRNA的表达

目的检测脊髓性肌萎缩症（SMA）患者神经元样细胞SMN2基因mRNA的表达。方法用PCR-RFLP的方法对SMA患者进行基因诊断,诱导其骨髓间充质干细胞分化为神经元样细胞,RT-PCR和测序检测该细胞SMN2基因mRNA的表达,所有过程与对照组进行对比研究。结果SMN2基因的扩增产物为全长转录产物fl-SMNmRNA（266bp）和转录时跳过外显子7的产物SMN△7mRNA（212bp,经测序证实缺少的54bp为外显子7的序列）;SMA患者fl-SMNmRNA的表达占总表达量的23．2％,远低于对照者（占总表达量的82．0％）;而SMN△7mRNA表达占总表达量的76．8％,高于对照者的18．0％。结论SMA患者神经元样细胞的SMN2基因转录时存在选择性剪接,即剪接时跳过外显子7,是导致其全长SMN蛋白不足的原因之一。     

遗传性主动脉疾病的基因组测序——400例患者的基因突变分析

目的 对遗传性主动脉疾病（HAD）患者多个相关基因进行检测分型及基因突变分析。方法 依据主动脉疾病基因检测推荐指南,筛查了2017年以来收治的400例疑似HAD患者,对已知的15个HAD候选基因进行二代测序,然后进行Sanger测序验证。若二代测序结果为阴性时,如先证者临床指征明显或有家族史,则考虑大片段缺失/插入检测或全外显子检测,根据检测结果进行统计分析。结果 纳入的400例患者中,204例（50.3%）患者共检测出235个可报告变异位点,主要以FBN1位点突变（136个,57.9%）较为常见,其余均为其他基因的罕见突变。400例患者中,121例（30.25%）为（可能）致病性突变,196例（49.00%）为（可能良性/良性）或无突变,其余83例（20.75%）均为临床意义未明的突变。而对临床指征明显或有家族史的13例患者的大片段缺失/插入检测结果显示,其中9例结果为阳性。结论 基于二代测序方法有效地检测出半数患者存在基因突变,且有30.25%的患者可明确其基因致病性,20.75%的患者突变基因尚待更多的循证医学数据进行验证。本研究不仅有助于临床医师早期鉴别诊断疾病类型,为患者实行...     

甲状腺髓样癌的诊断与筛查

大部分遗传性甲状腺髓样癌的患者具有ret原癌基因的突变，因此对有遗传倾向的个体进行基因检测，就可进行早期诊断与筛查，并有利于早期治疗，改善预后。本文主要阐述了目前已发现的ret原癌基因的突变与甲状腺髓样癌的关系，并探讨基因检测在甲状腺髓样癌早期诊断中的应用，以及甲状腺髓样癌的诊断方法。     

Diabetes coexistent with Charcot–Marie–Tooth disease presenting as a recurrent foot ulcer misdiagnosed as diabetic foot: A case report

Both diabetes mellitus and Charcot–Marie–Tooth disease (CMT) can lead to severe peripheral neuropathy. The differential diagnosis of peripheral neuropathy is difficult due to the similar clinical features. There are still some clues, such as unusual muscle atrophy, unmatched severity of peripheral neurogenic damage with nephropathy or retinopathy, which could alert clinicians to make differential diagnosis. Although diabetes mellitus is rarely concurrent with CMT, it will exacerbate clinical disorders in patients with CMT. To date, there is no specific medicine for CMT treatment. Offloading devices and desirable comprehensive management of diabetes mellitus might be beneficial to avoid plantar ulcer recurrence and anti-progression of CMT.     

肥厚型心肌病样临床表现的Fabry病家系研究

目的对一个临床表现酷似肥厚型心肌病的Fabry病家系进行α-半乳糖苷酶（α-GalA）基因测序并发现其突变形式。方法该家系成员共15例,经过询问病史、体格检查、心电图及超声心动图检查,抽取外周静脉血标本,提取白细胞基因组DNA,PCR分段扩增α-GalA基因的7个外显子序列,产物纯化后直接测序,分析筛查基因的突变位点。结果家系中有9例发生α-GalA基因新的错义突变,突变位点位于α-GalA基因第5外显子的第32号密码子,均由TGG变为TGA,TGA为终止密码子,故可引起TGG正常编码的色氨酸残基编码中断。其中6例女性为带有突变基因的杂合子,3例男性为带有突变基因的半合子。9例患者中6例患有心肌肥厚。家系中正常人无此类突变。结论对心肌肥厚患者应与Fabry病进行鉴别诊断。α-GalA基因突变检测可用于Fabry病患者及其亲属,以明确诊断和进行病因学治疗。     

相同基因型而不同表现型的PRKAG2基因突变一家系报道

目的 位于7号染色体上的腺苷一磷酸激活的蛋白激酶γ^2调节亚单位基因（PRKAG2基因）调节代谢通路。报道一个具有PRKAG2基因突变而临床表现型不同的家系。方法 使用DNA直接测序法,对一个具有多种形式心律失常的患者家系（13例患者）进行PRKAG2外显子及外显子和内含子拼接部位序列筛查寻找基因突变。结果 心电图显示患者家系存在窦性心动过缓、短PR间期、完全性右束支传导阻滞、房室传导阻滞和房性心动过速。其中3例患者在年轻时发生猝死,没有1例有预激综合征（预激）表现,只有1例有心肌肥厚。DNA测序结果显示,该家系所有患者皆有一个PRKAG2错义突变（R302Q）。这个基因突变以前曾描述并与预激和左室肥厚有关。结论 PRKAG2基因突变不仅导致预激而且与多种临床表现型有关。完全性右束支传导阻滞、窦性心动过缓、短PR间期应该高度怀疑有PRKAG2基因突变的可能。     

基因突变与遗传性内分泌代谢性疾病

遗传性内分泌代谢性疾病是内分泌代谢疾病中相当重要的一组疾病,临床表现复杂多变,诊治困难。遗传性内分泌代谢性疾病的分子基础是其相关基因发生突变,近年随着分子生物学技术的飞速发展,相当多的致病基因被发现,人们对此类疾病的理解逐步深入,同时也为临床诊断提供了快速准确的技术平台。本文将根据致病基因功能,对近年来遗传性内分泌代谢性疾病取得的进展进行阐述。     

间隙连接蛋白37基因C1019T多态性和冠心病的关系

目的:研究皖北地区汉族人群中间隙连接蛋白37(connexin37)基因C1019T多态性与冠心病的相关性。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)结合琼脂糖凝胶电泳检测技术分析106例冠心病患者(其中心绞痛57例,心肌梗塞49例,均经冠状动脉造影证实),和38例冠状动脉造影无明显异常者(对照组)的connexin37基因C1019T多态性位点基因型和等位基因频率分布,同时将冠心病组分为心绞痛和心肌梗塞两组分别与对照组相比较。结果:在心肌梗塞组与对照组的基因型和等位基因频率分布比较中,connexin37C1019T基因型(CC型、CT型和TT型)在心肌梗塞组中分布频率分别为49.0%,30.6%,20.4%,在对照组中为15.8%,42.1%,42.1%,有明显差异(P=0.004);C等位基因(CC+CT)频率在两组中分别为(61.5%:40.7%,P=0.024)。在性别亚分组分析比较中,男性人群的CC基因型和C等位基因频率在心肌梗塞组中明显高于对照组(CC基因型:56.0%:16.7%,P=0.0014,C等位基因频率:66.7%:40.0%,P=0.043),而女性心肌梗塞组中未发现上述明显差异。另外在心绞痛组和对照组基因型、等位基因频率分析比较中也未发现差异有显著性。结论:皖北地区汉族男性的CC基因型和C等位基因可能与心肌梗塞发生有相关性。     

LMNA‐Mediated Arrhythmogenic Right Ventricular Cardiomyopathy and Charcot‐Marie‐Tooth Type 2B1: A Patient‐Discovered Unifying Diagnosis

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an uncommon cardiomyopathy most classically associated with mutations in genes encoding desmosomal proteins. Recent literature has identified mutations in several non‐desmosomal proteins including lamins that may result in the ARVC phenotype. We describe a patient who discovered her own pathogenic LMNA mutation that offered a unifying diagnosis explaining her ARVC and Charcot‐Marie‐Tooth phenotypes as well as musculoskeletal abnormalities. Suspicion for LMNA‐mediated cardiomyopathy should arise in patients with extracardiac manifestations of laminopathies and testing for specific gene mutations may be helpful in establishing an unifying diagnosis.     

Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis

BACKGROUND: Insulin resistance is a key feature of nonalcoholic fatty liver disease. Patients with hereditary hemochromatosis, a disease characterized by progressive iron overload due, in most cases, to homozygosity for C282Y mutation in the HFE gene, have often decreased insulin sensitivity and release. AIMS: To determine whether increased iron parameters/heterozygosity for the mutations of the HFE gene confer susceptibility to nonalcoholic fatty liver disease. PATIENTS: One hundred and thirty-four consecutive Italian patients with clinical and ultrasonographic diagnosis of nonalcoholic fatty liver disease (82 with hyperferritinemia), half confirmed by liver biopsy. METHODS: Insulin was determined by radioimmunoassay. HFE gene mutations were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: (1) Prevalence of C282Y HFE mutation was significantly higher in patients with nonalcoholic fatty liver disease compared to controls, the difference being more striking in patients with hyperferritinemia than in those without. (2) The presence of mild iron overload was associated with a lower insulin release. (3) Carriers of C282Y mutation developed nonalcoholic fatty liver disease despite lower body mass index and triglycerides. CONCLUSION: The mild iron overload associated with heterozygosity for C282Y HFE mutation confers susceptibility to nonalcoholic fatty liver disease, causing relative insulin deficiency.     

Identification of a novel mutation in CYBB gene in a Chinese neonate with X-linked chronic granulomatous disease: A case report

Rationale:X-linked chronic granulomatous disease (X-CGD) is an X-linked recessive disorder of the Nicotinamide adenine dinucleotide phosphate oxidase system that can cause primary immunodeficiency. Mutations in the CYBB gene located in Xp21.1 were accounting for X-CGD disease. More than 600 mutations have been identified as the cause of X-CGD in various populations worldwide.Patient concerns and diagnosis:In this study, the proband suffered from elevated white blood cells (WBC, 23.65 × 109/L), mainly in neutral (16.4 × 109/L). The neutrophil oxidative index of the patient was 2.13, which was extremely low, whereas his mother was 69.0 (Ref >100). Next, next-generation sequencing of the primary immunodeficiency diseases -related gene panel was performed. One novel mutation was identified in the CYBB gene in the CGD case: c.55C>G in exon 2. The mutation was verified by Sanger sequencing. The mother of the patient was heterozygous for the c.55C>G mutation, and the father was normal. These mutations were not present in the 100 unrelated normal controls.Interventions and outcomes:The patient died from severe and uncontrollable pulmonary infection at 3 months of age.Lessons:The identification of these mutations in this study further expands the spectrum of known CYBB gene mutations and contributes to the genetic counseling and prenatal molecular diagnosis of X-CGD.     

纤维蛋白原α链剪切位点IVS2＋1G〉C突变导致的遗传性低纤维蛋白原血症

目的：探讨遗传性低纤维蛋白原（Fg）血症的分子发病机制。方法：检测凝血指标以明确诊断；用DNA直接测序法对患者Fg基因FGA、FGB和FGG的所有外显子及其侧翼序列进行测序以寻找基因突变，对有突变的序列反向测序证实；通过逆转录结合巢式PCR扩增的方法，检测患者外周血中的Fg异位转录产物；构建含有突变点的突变型FGA小基因（minigene）质粒和野生型FGA小基因质粒，将2种质粒分别转染人胚肾（HEK）293T细胞，抽提RNA．逆转录PCR（RT—PCR）后TA克隆测序。结果：先证者呈FGA基因剪切位点IVS2＋1G〉C杂合突变；对于该突变，逆转录结合巢式PCR的产物经克隆后测序只检测到正常转录本，而没有发现异常转录本：突变型FGA小基因质粒转染HEK293T细胞后．抽提RNA再经RT-PCR、TA克隆、测序，揭示剪接过程中发生了FGA基因2号内含子滞留，导致终止密码的提前出现．从而使异常转录的mRNA在体内很快被降解。结论：异位转录结合体外表达证明先证者FGA基因剪切位点IVS2＋1G〉C突变导致异常转录mRNA在体内很快被降解，是先证者低Fg血症的原因之一。