一个肾上腺脑白质营养不良家系的ABCD1基因突变分析

目的 通过对1例疑似肾上腺脑白质营养不良(ALD)患者及该家系其他成员进行ALD基因分析来明确诊断. 方法 从患者和家庭成员的外周血白细胞提取总RNA和基因组DNA:应用RT-PCR技术,首先对先证者cDNA的ABCD1基因编码区进行序列分析,寻找突变位点,再通过PCR和直接测序等方法 进一步确证该突变位点;同时对该家系其他成员的相应基因组DNA进行ABCD1基因分析. 结果 先证者的ABCD1基因第656(G)、657(A)位碱基缺失,造成移码突变fs R89,可以确诊为ALD.该家系其他成员基因突变分析结果 为:先证者表弟存在与先证者相同的突变,为ALD半合子;先证者的母亲、小姨、表妹均为ALD携带者;先证者姐姐为ABCD1正常基因型. 结论 在中国人ALD患者中发现了1个新的ABCD1基因突变(fs R89),ABCD1基因突变分析是诊断X-ALD最可靠的方法 .     

肾上腺脑白质营养不良2例

肾上腺脑白质营养不良（AdrenoleukodystrophyALD）是罕见的X连锁隐性遗传脂质代谢病,预后不良。自从MRI技术在小儿神经病应用以来,并结合临床及实验室检查．本病较前容易诊断。笔者特报告2例,并进行讨论。l、病例摘要例一、男,5岁,因反复惊厥1年入院。患儿子2岁开始面部外生殖器皮肤颜色逐渐加深,2岁半时又开始智力逐渐落后,且已形成的智力开始倒退,言语断续而含糊,行走困难,1年来,又有惊厥,以四肢抽动为主,不呕吐,不伴发热。查体：神志清,反应迟钝,站立不稳,不能行走。全身皮肤颜色呈褐色,无皮疹,面部对称,四肢肌…     

肾上腺脑白质营养不良的临床表现

目的:报告2例肾上腺脑白质营养不良病例及其家系调查。方法:复习2例临床资料,结合文献进行分析。结果:肾上腺脑白质营养不良可有多种临床类型,起病于儿童的进行性精神迟滞、视力障碍及肾上腺皮质功能减退,应考虑到肾上腺脑白质营养不良的可能。结论:肾上腺脑白质营养不良的诊断需要结合临床表现及影像学检查,尤其是血中含C2 2 以上极长链饱和脂肪酸的水平增高是确诊的重要依据。其治疗以骨髓移植疗效较肯定,基因治疗尚待进一步探讨。     

肾上腺脑白质营养不良1例报告

患儿 ,男 ,5岁 ,因四肢不自主抽动 ,易摔跤 2年来诊。患儿足月顺产。 3岁会走路、说话 ,走路时右腿拖动易摔跤 ,跑跳较同龄儿慢 ,伴四肢不自主抽动 ,症状渐加重。无智能及视力障碍。家族史 :父母非近亲结婚 ,父亲 2 0岁时右上肢亦不自主抽动 ,且面色发黑、智能稍差。查体 :神清 ,体格发育正常 ,头颅及面部器官无畸型 ,全身皮肤色深 ,面部尤重 ,血压6 0 / 40 mm Hg,肝脾不大。智能正常 ,颅神经正常 ,可见四肢肌阵挛 ,双下肢肌力 4级 ,双上肢肌力正常 ,四肢肌张力正常 ,共济无异常 ,深浅感觉无异常 ,双侧跟、膝腱反射亢进 ,右Babinski's( +) …     

肾上腺脑白质营养不良的临床特征

目的探讨肾上腺脑白质营养不良（ALD）的临床特征。方法对4例男性ALD患者的临床资料进行回顾性分析。结果发病年龄7～11岁,均有智能下降、肢体无力,3例伴言语不清、共济失调,2例伴视听力下降,1例伴视神经萎缩、癫痈发作,血睾酮降低及血17-羟类固醇降低各1例,B超示双侧睾丸弥漫性病变、脑活检示类脂质沉积病各1例,4例磁共振（MRI）均见双侧枕项叶对称性蝶翼状长T1、长T2信号灶,可累及颞叶、内囊和脑干白质。结论ALD以儿童脑型常见,主要表现为智能下降、肢体无力、言语不清、共济失调、视听力下降及癫痈发作等症状,可伴有视神经萎缩、肾上腺皮质及睾丸损害,依据临床症状和典型的MRI表现可以进行临床诊断。     

肾上腺脑白质营养不良的研究进展

肾上腺脑白质营养不良(ALD)是最常见的先天性过氧化物酶体疾病,本文对其近几年在病因、病理、发病机制、临床表现、辅助检查及治疗方法的研究进展作一综述。     

X-连锁的肾上腺脑白质营养不良1家系报道

肾上腺脑白质营养不良(X-ALD)是以进行性脑功能障碍和肾上腺皮质功能减退为特点的一类遗传性脂肪酸代谢障碍性疾病。分子生物学研究发现该病的致病基因位于Xq28,由ABCD1基因突变引起。目前研究认为该病与过氧化物酶和转运酰基辅酶A的转运蛋白有关,过氧化物酶缺乏可导致极长链脂肪酸(VLCFAs)在脑白质和肾上腺皮     

成人肾上腺脑白质营养不良

报道２例经病理证实的成人肾上腺脑白质营养不良病例。患者均呈进行性痴呆、皮质盲、去皮层状态。分别于病后６个月、１８个月死亡。例１行脑组织极长链脂肪酸含量及其比值测定。结果明显高于对照组，从而肯定了诊断。     

肾上腺脑白质营养不良l家族报告

肾上腺脑白质营养不良是一种罕见的伴性隐性遗传病 ,在我国发病率很低 ,现报导 1家族如下。患者 ,男 ,11岁 ,因目光呆滞 4个月 ,性格改变、小便异常 3个月入院。 4个月前无明显诱因 ,经常出现向左侧歪头、凝视 ,无其它不适 ,家长未在意。 3个月前性格变得古怪、好动 ,常钻入父母怀抱 ,喜被抚摸 ,夜晚尿床 ,白天尿急 (有便意时常来不及脱裤 ,小便已流出 ) ,并出现言语不流利。左侧枕部头痛、喷射样呕吐胃内容物一次。曾到多家医院就诊治疗无效果 ,10天前因发热 ,在村卫生室诊断为肺炎 ,给予青霉素抗炎治疗后 ,小便转为正常。 5天前呕吐胃内容…     

肾上腺脑白质营养不良一例

1病例报告患儿男性,10岁,因"渐进性智能减退13个月,吞咽困难1个月"于2009年9月15日入作者医院。2008年8月患儿学习成绩下降,近记忆力减退,敏感、暴躁,间断哭闹,视力、听力均减退,言语减少;同年11月出现     

中国肾上腺脑白质营养不良患者中一个新的ABCD1基因突变的鉴定

目的鉴定并分析1个新的肾上腺脑白质营养不良家系的基因突变类型和位点.方法采用长链RT-PCR技术,从外周血提取总RNA并合成cDNA,以cDNA为模板,分4个片段扩增致病基因编码区,将纯化后的PCR产物直接测序,找出基因突变的位点.同时应用限制性酶切分析的方法,分析发病家系所有成员的基因组DNA,以证实所发现的突变.结果患者肾上腺脑白质营养不良基因外显子2上的第343位密码子发生了GGC→GTC改变,使原来编码的甘氨酸被缬氨酸(G343V)取代;患者母亲为G343V突变携带者,患者哥哥的基因型和患者完全相同,其父亲为正常基因型.结论在中国人肾上腺脑白质营养不良患者中发现一个新的ABCD1基因突变,即G343V突变.     

Prenatal diagnosis of citrullinemia type 1: A Chinese family with a novel mutation of the ASS1 gene

Background

Argininosuccinate synthetase deficiency (citrullinemia type 1) is a rare autosomal recessive disorder of the urea cycle characterized by elevated concentrations of citrulline, ammonia, and orotic acid, manifesting with acute hyperammonemic crises, usually early in life, with concurrent neurologic deterioration. Only a few cases of citrullinemia type 1 have been documented from mainland China. Prenatal diagnosis has not been performed.

Methods

A Chinese family affected by citrullinemia type 1 was studied. The proband, a girl, was the second child born to a non-consanguineous couple. Her elder brother died at 19 months due to coma and liver dysfunction of unknown cause. The proband was admitted because of severe mental retardation and lethargy at the age of 15 months. Initial laboratory results revealed hyperammonaemia, hypercitrullinemia (928.771 μmol/L, normal 5.0–25.0 μmol/L) and orotic aciduria, supporting the diagnosis of citrullinemia type 1. Subsequently, the mother presented at 15 weeks of pregnancy seeking for genetic counseling and prenatal diagnosis. ASS1 gene in the blood leukocytes of the family members and amniocytes was performed by direct sequencing.

Results

On the ASS1 gene of the proband, a novel mutation, T1009C (C337R), and a previously reported mutation G847A (E283K) were identified. Each parent carries one of two mutations. G847A and T1009C mutations were detected in amniocytes, as same as the proband of the family. The result revealed that the fetus was affected by argininosuccinate synthetase deficiency. The parents chose to have a termination of the pregnancy.

Conclusions

Prenatal diagnosis for citrullinemia type 1 was performed in a Chinese family using gene analysis. T1009C (C337R), a novel mutation of ASS1, was identified.     

基于脐带血和短串联重复序列分析的脊髓小脑共济失调3型产前诊断

目的 探讨脊髓小脑共济失调3型(SCA3)的产前诊断方法 .方法 对1个SCA3家系女性先证者的胎儿进行产前检测,于妊娠20周抽取脐带血进行胎儿DNA提取,采用PCR和基于CEQ8000核酸分析仪的短串联重复序列分析技术进行SCA3基因CAG重复序列动态突变检测.结果 先证者SCA3基因CAG重复数目为31/75次,其配偶CAG重复数目为14/27次,胎儿CAG重复数目为14/31次,其中14次重复来自父亲,31次重复来自母亲的正常等位基因,符合孟德尔遗传规律.本次检测的胎儿携带患者的正常等位基因.胎儿出生后的检测结果 与产前检测完全相同.结论 通过脐带血和短串联重复序列分析技术检测SCA3基因CAG重复序列动态突变,可快速、可靠地进行SCA3产前诊断.     

D uchenne 型肌营养不良家系的临床及分子遗传学研究

目的：探讨Duchenne型肌营养不良（DMD）家系的临床及分子遗传学特征。方法收集并分析我院收治的2个DMD家系临床资料和基因检测结果,并结合既往相关文献,回顾该病在临床表现、分子遗传学等方面的特点。结果DMD儿童期隐匿起病,进行性加重,以肌无力、肌萎缩为特点,可伴肌肉假性肥大,血清肌酶水平异常增高,肌电图呈肌源性损害,肌肉活检呈肌病特征。本文报道的2个家系经基因检测家系1先证者为DMD基因的第3～21号外显子缺失,家系2先证者则为第8、9外显子重复突变,2个家系中的先证者基因均为纯合突变,且其母亲均为致病基因的携带者,符合X染色体隐性遗传的规律。结论早期识别DMD的临床特征有助于提高该病的诊断水平,基因检测是一种确诊DMD快速、有效的方法。     

脊髓小脑共济失调3型家系CAG动态突变分析和产前诊断

目的探讨脊髓小脑共济失调3型患者的临床特点、分子遗传学特征及产前诊断的意义。方法采用聚合酶链反应及DNA片段分析技术对脊髓小脑共济失调3型一家系4代共9例患者（其中1例为先证者之4月龄胎儿）中的2例患者施行SCA3／ATXN3基因（CAG）。重复数目分析。结果一家系中4代共9例患者发病均符合常染色体显性遗传特征,其中8例患者（除外先证者之4月龄胎儿）均以步态不稳为首发症状,伴发不同程度构音障碍;先证者神经系统检查显示共济失调伴眼球上视受限及锥体束损害体征。其中第1代患者于50岁左右发病、第2代患者40～45岁发病、第3代（先证者）28岁发病,发病年龄呈逐代提前现象。先证者SCA3／ATXN3基因（CAG）。重复数目为77次（〉44次）,其4月龄胎儿（CAG）．;重复数目也为77次,通过产前诊断证实亦为脊髓小脑共济失调3型患者。结论脊髓小脑共济失调3型是亚洲人种中最常见的脊髓小脑共济失调亚型,以步态不稳为首发症状,除小脑性共济失调外尚可伴发其他临床表现。家系中存在遗传早现现象,但其CAG动态突变率较小。脊髓小脑共济失调3型病因明确但无有效治疗方法,对患者进行遗传咨询并对其胎儿进行产前诊断,是预防和中断遗传链之关键措施。     

Acute and long‐term response of dopamine nigrostriatal synapses to a single,low‐dose episode of 3‐nitropropionic acid‐mediated chemical hypoxia

The goal of the present investigation was to determine the persistence of striatal (DA) dopaminergic dysfunction after a mild chemically induced hypoxic event in Fisher 344 rats. To this end, we gave a single injection of the mitochondrial complex II inhibitor 3‐nitropropionic acid (3‐NP; 16.5 mg/kg, i.p.) to 2‐month old male F344 rats and measured various indices of striatal DA functioning and lipid peroxidation over a 3‐month span. Separate groups of rats were used to measure rod walking, evoked DA release, DA content, malondialdehyde (MDA) accumulation, DA receptor binding, and tyrosine hydroxylase (TH) activity. The results showed that 3‐NP exposure reduced most measures of DA functioning including motoric ability, DA release, and D₂ receptor densities for 1 to 3 months postdrug administration. Interestingly, DA content was reduced 1 week after 3‐NP exposure, but rose to 147% of control values 1 month after 3‐NP treatment. MDA accumulation, a measure of lipid peroxidation activity, was increased 24 h and 1 month after 3‐NP treatment. 3‐NP did not affect TH activity, suggesting that alterations in DA functioning were not the result of nigrostriatal terminal loss. These data demonstrate that a brief mild hypoxic episode caused by 3‐NP exposure has long‐term detrimental effects on the functioning of the nigrostriatal DA system. Synapse, 2011. © 2010 Wiley‐Liss, Inc.     

Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model

While we recently reported the beneficial effects of omega-3 polyunsaturated fatty acids (n−3 PUFAs) in a mouse model of Parkinson's disease (PD), the mechanisms of action remain largely unknown. Here, we specifically investigated the contribution of the brain-derived neurotrophic factor (BDNF) to the neuroprotective effect of n−3 PUFA observed in a mouse model of PD generated by a subacute exposure to MPTP using a total of 7 doses of 20 mg/kg over 5 days. The ten-month high n−3 PUFA treatment which preceded the MPTP exposure induced an increase of BDNF mRNA expression in the striatum, but not in the motor cortex of animals fed the high n−3 PUFA diet. In contrast, n−3 PUFA treatment increased BDNF protein levels in the motor cortex of MPTP-treated mice, an effect not observed in vehicle-treated mice. The mRNA expression of the high-affinity BDNF receptor tropomyosin-related kinase B (TrkB) was increased in the striatum of MPTP-treated mice fed the high n−3 PUFA diet compared to vehicle and MPTP-treated mice on the control diet and to vehicle mice on the high n−3 PUFA diet. These data suggest that the modulation of BDNF expression contributes, in part, to n−3 PUFA-induced neuroprotection in an animal model of PD.