一例Rett综合征患儿多种组织的线粒体DNA突变分析

一例Ｒｅｔ综合征患儿多种组织的线粒体ＤＮＡ突变分析唐炬包新华戚豫吴希如作者单位：１０００３４北京医科大学第一医院儿科Ｒｅｔ综合征（Ｒｅｔｓｙｎｄｒｏｍｅ）是一种严重影响儿童精神、运动发育的神经系统遗传性疾病。既往有关该病的遗传学研究多集中在Ｘ染色体上...     

Rett综合征的X染色体失活类型及其线粒体DNA的初步研究

对１９例Ｒｅｔｔ综合征患儿进行了临床随访及家族史调查，并利用Ｓｏｕｔｈｅｒｎ杂交及聚合酶链反应技术，对１２例患儿和１１例患儿母亲的Ｘ染色体失活类型及８例患儿的线粒体ＤＮＡ的部分区域进行了初步研究。结果显示，患儿母亲的流产率及死胎率无增高；患儿及母亲的Ｘ染色体非随机失活的比率较高，３例Ｘ染色体非随机失活的母亲均将其失活的Ｘ染色体遗传给患儿，提示Ｘ染色体非随机失活在该病的遗传过程中起一定作用；未发现线粒体ＤＮＡ有大的缺失。以上工作尚需更多病例加以证实。     

Rett综合征的临床特点及MECP2基因突变分析

目的 分析典型的Rett综合征患者的临床特点,并对患儿甲基化CpG结合蛋白-2（MECP2）基因进行突变分析。方法 使用PCR扩增和测序的方法 对近期诊断的9例RETT综合征患儿及其父母MECP2基因的3个外显子进行检测。结果 在9例患儿中发现5例存在MECP2基因的杂合突变,突变率超过50%,其中1例为碱基插入导致的移码突变（c.913insT）;其余4例为点突变,分别为位于外显子3的c.316C>T（R106W）,位于外显子4的c.502C>T（R168X）、c.808C>T（R270X）和c.1126C>T（P376S）,其中c.913insT为首次发现的突变,这些患儿父母均未检测到突变。2例患儿MECP2基因突变位于转录抑制区域,与其他患儿相比,这2个患儿语言功能几乎丧失,且发育明显落后。结论 该研究确诊的5例Rett综合征的患儿存在MECP2基因突变,且多数位于外显子4上;MECP2蛋白转录抑制区域突变可能影响患儿语言功能及发育明显落后。     

猫叫综合征六例临床和细胞遗传学研究

猫叫综合征六例临床和细胞遗传学研究王世雄周文浩胡琴黄荣魁作者单位：２０００９２上海市儿科医学研究所猫叫综合征（ｃａｔｃｒｙｓｙｎｄｒｏｍｅ，或ｃｒｉｄｕｃｈａｔｓｙｎ－ｄｒｏｍｅ）是第５号染色体短臂部分缺失所引起的少见染色体病，又称５Ｐ－综合征，１９...     

Rett综合征2例报道

<正> 例1,患儿,女,2岁1个月。因“发现精神、运动发育落后18个月,双上肢抽动14个月”入院。患儿第1胎,第1产,胎龄39周,足月顺产,无缺氧窒息史。出生体重3 100 g,头围33.5 cm。患儿7个月前神经、精神、行为发育正常。3个月会抬头。4个月可从俯卧翻至仰卧。6个月能独坐,双手能握奶瓶,会玩自己的脚,能自己拿饼干吃,能发“ba、ka、”等音节,当母亲抱时能伸直上臂,喜欢玩“藏猫猫”游戏,能模仿动作和声音。7个月后家人开始发现患儿发育倒退,渐渐不能独坐,双手出现无意识、无目     

Rett综合征男童1例

患儿,男,5岁6个月,因智力减退、语言障碍伴手刻板运动2年余入我院。患儿生后无反复呕吐及喂养困难病史,运动、智力发育正常。2岁9个月开始出现手刻板动作,如拍手、拍头、捂耳等,并逐渐加重,说话渐减少,至语言能力丧失,对外界无兴趣,但眼对眼交流存在。病后情绪喜怒无常,伴凝视、傻笑、尖叫、偏激等异常行为。运动功能稍减退,上肢能主动拿物,能自己进食,但不稳。无昏迷、惊厥,无过度换气和屏气发作。家族中无类似病史。查体:头围5 2cm ,心、肺、腹未见异常。神经系统检查:神清,肌力、肌张力正常,无不自主运动、共济失调,双膝腱、跟腱反射减弱…     

Rett综合征患儿MECP2基因型和表型关系研究

目的 寻找中国Rett综合征(RTT)患儿甲基化CpG结合蛋白2基因(MECP2)突变的基因型和表型之间的相互关系,为临床诊断和治疗提供帮助.方法 对126例经分子遗传学方法诊断的RTT患儿的临床表型参照Kerr等和Scala等评分标准进行打分,采用SPSS 12.0软件包进行统计分析.结果 分析MECP2突变类型、基因功能区和表型的关系显示,位于基因不同功能区的突变:甲基化CpG结合区(MBD)、转录抑制区(TRD)和C末端(CTS)对RTT表型的影响差异无统计学意义(P>0.05);不同突变类型:错义、无义、移码和大片段缺失突变对RTT表型的影响差异无统计学意义(P>0.05).分析MECP2突变类型和基因功能区共同对表型的影响显示:同位于MBD的无义和错义突变相比较,前者临床严重性评分高于后者,差异有统计学意义(P=0.016),而位于TRD的无义和错义突变临床严重性评分之间差异无统计学意义(P>0.05);位于MBD和TRD的错义突变的临床严重性评分之间差异无统计学意义(P>0.05),位于MBD和TRD的无义突变的临床严重性评分之间差异无统计学意义(P>0.05).分析MECP2最常见突变类型和表型的关系显示:p.T158M、p.R168X、c.806delG和p.R255X对RTT表型总的影响差异无统计学意义(P>0.05),但在语言功能的受累程度上,以上4种突变之间差异有统计学意义(P=0.028),且语言能力受损的发生率差异也有统计学意义(P=0.019).结论 MECP2基因型和表型之间存在一些相互关系:位于MBD的无义突变病情较严重;在<5岁组中发生频率较高的4种突变对语言功能和语言能力受损发生率方面存在不同,其中p.R168X受损最重.     

Rett综合征的诊断与治疗

Rett综合征（RS）作为一种严重影响儿童精神运动发育的非神经系统退化性疾病，自发现以来得到了国际医学领域的广泛关注。由于临床表型及其严重性具有显著异质性，且无特异性检测指标，RS的诊断与治疗仍有一定难度。现对RS的发病机制、临床表现及其诊断标准的变化与治疗作一简要介绍，以期加深临床医师对RS诊断标准及治疗方案的认识。     

Rett综合征与MECP2基因

Rett综合征是一种严重影响儿童精神运动发育的神经遗传病 ,诊断主要依靠国际上根据临床表现制定的标准 ,包括典型和非典型Rett综合征两类。该病的遗传方式尚无定论。致病基因是位于染色体Xq2 8的MECP2基因 ,编码甲基化结合蛋白 2。推测致病机制为MECP2基因突变导致蛋白结构和功能异常 ,使胚胎发育时期应当转录静止的基因继续转录 ,而这种“转录噪音”对神经系统的生长和发育具有致病作用。典型Rett综合征患儿MECP2基因主要有 8种热点突变。MECP2基因作用的下游靶基因尚不清楚。     

Rett综合征合并Chiari畸形男童1例并文献复习

Rett综合征(Rett syndrome,RTT)是一种严重影响儿童精神运动发育的X连锁显性遗传疾病,1966年由AndreasRett最先报道。发病率为1/万,女孩多见。RTT的发生通常不伴有其他先天畸形[1]。Chiari畸形与RTT联合发生的病例,在国内尚未查到文献报道。1临床资料患儿男,5岁,因“发作性抽搐     

Rett syndrome

Rett syndrome is a progressive neurodegenerative disease of unknown etiology. Reported here are three children who presented with all clinical features of Rett syndrome. The aim of this presentation is to alert physicians to the existence of this progressive brain disease which only affects girls and so far no specific treatment has been suggested.     

Growth and nutrition in 10 girls with Rett syndrome

Cross-sectional and retrospective data on growth and anthropometric outcome, feeding problems and dietary intake are presented for 10 girls between three and 16 years of age with Rett syndrome. All girls had birth weight and length within the normal range for gestational age and development was considered normal until six to 24 months of age. The girls presented a fall off in linear growth during the first two years of life and at the time of study, all but one had height and/or weight for height below the 2.5th percentile of healthy children. The girls had good appetite but could not eat by themselves and oral-motor dysfunctions were common. The mean energy intake was 66.9% of the US recommendations according to age and 107.8% of the recommendations according to body weight. The intakes of thiamin, vitamin D, calcium and iron were considered low. None was anaemic. Different nutritional intervention strategies should be investigated to reduce and, if possible, prevent malnutrition and wasting in girls with Rett syndrome.     

Rett syndrome in a patient with medium chain acyl-CoA dehydrogenase deficiency

A female patient with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency developed normally until 13 months of age after which she showed a gradual developmental delay, followed by progressive dementia, and a decrease in head circumference growth culminating in the diagnosis of Rett syndrome at 3.5 years.     

Challenges in evaluating the oculomotor function in individuals with Rett syndrome using electronystagmography

Background

Rett syndrome (RTT) is a neurological disorder characterized by a broad spectrum of symptoms. Communication is a major area of difficulty. Use of eye tracking technology offers a potentially effective method of communication when underpinned by intact oculomotor function. In this study, oculomotor function was assessed using electronystagmography (ENG). However, challenges were encountered when examining individuals with RTT.

Rett syndrome revisited: A patient with biotin dependency

A patient with Rett syndrome (cerebral atrophy associated with hyperammonemia) was studied. Primary defects of urea cycle enzymes were excluded as causes of the disorder. The analysis of urinary organic acids showed a moderate increase of lactate, methylcitrate, tiglylglycine and 3-hydroxisovalerate, indicating an abnormality of multiple carboxylases. Biotin supplementation reversed the urinary abnormalities. In fibroblasts grown with a low biotin medium propionylCoA and 3-methylcrotonylCoA carboxylase activities were reduced. Holocarboxylase synthetase activity was normal (V _max and K_m). Surprisingly the biotinidase in fibroblasts was not decreased. The data indicate that some patients with Rett syndrome might suffer from a biotin-dependent defect of unknown nature.     

Head growth in Rett syndrome

The longitudinal development of head growth was investigated in girls with Rett syndrome. Measurements were taken retrospectively from different kinds of records. Growth retardation was expressed in standard deviation (SD) scores. In classic types, the mean head circumference fell successively to 2 SD scores below the norm at the age of 4 y. After the age of 8 y it stabilized close to -3 SD scores. The degree of deceleration correlated strongly to the age at which a deceleration of 1 SD score had occurred. In forme fruste variants, the mean head circumference was within normal limits; however, it was significantly below the norm (-0.8 SD scores). Body height deviated to -2 SD scores at the age of 6 y and was highly correlated to decline in head growth. When head growth was related to the severity of motor disability, there was a continuum from almost normal head growth with well-preserved gross motor function and some preserved fine motor function to a marked deceleration in head growth with maximum gross and fine motor disability.     

Family data in Rett syndrome: association with other genetic disorders

BACKGROUND: Rett syndrome is a neurological disorder, almost exclusively affecting girls. METHODOLOGY: Between 1993 and 1995 pedigree data were obtained from families of girls registered with the Australian Rett syndrome database. RESULTS: Although 21 individual disorders were reported to be present in family members of affected girls, there was no apparent clustering of the same disorder in different families. However it was certain that a geneticist had been involved in only 10.9% of cases. CONCLUSIONS: Mutations in the MECP2 gene have now been reported in a proportion of sporadic cases. Thus, it will be important to examine this phenotype-genotype correlation in the Australian cohort. Where a mutation is found, prenatal diagnosis in a subsequent pregnancy will be a possibility. Using the Australian population database and in conjunction with the clinical genetic services in each state it is planned to contact families with an affected girl to offer testing and counselling.     

Polysomnographic findings in Rett syndrome

Introduction

Rett syndrome (RS) is a severe neurodevelopment disorder associated with abnormal breathing during wakefulness and disturbed nocturnal behaviour. Breathing abnormalities during daytime have been extensively reported but polysomnographic (PSG) findings have been poorly studied.