Aicardi-Goutières 综合征 4 型 1 例临床和基因分析

目的探讨Aicardi-Goutières综合征(AGS)的临床、影像及遗传学特点。方法回顾分析1例AGS 4型患儿的临床资料及二代基因测序结果,并复习相关文献。结果患儿,女,5个月,临床表现为反复发热,精神运动发育落后,癫痫,小头畸形,痉挛状态。脑脊液淋巴细胞增多;头颅磁共振成像示脑萎缩、脑白质异常;头颅CT示双侧基底节区及脑白质钙化。基因检测发现RNASEH2A基因存在c.199GC、c.322CT复合杂合突变;c.322CT致病性已有文献报道,与AGS 4型相关;c.199 GC致病性尚未见文献报道。结论首次报道我国RNASEH2A基因变异所致AGS。     

Aicardi-Goutières 综合征 6 型 1 例临床及家系基因分析

目的探讨Aicardi-Goutières(AGS)6型的临床、影像及基因型特点。方法回顾分析1例AGS6型患儿的临床资料,并复习相关文献。结果先证者,男,11岁,自幼发育落后,因抽搐就诊。颈部和手足背面对称性混杂的色素沉着和色素脱失斑,面部雀斑样色素斑。头颅CT提示双侧基底节区钙化灶;头颅MRI示胼胝体薄,两侧内囊及外囊、脑室白质旁、半卵圆中心白质广泛异常信号。基因测序提示ADAR复合杂合突变,突变位点为c.1AG和c.3124CT,国内未见报道。先证者哥哥携带同样的基因突变,临床仅有皮损表现,父母表型正常。结论报道我国首例ADAR基因突变导致的AGS 6型。ADAR基因表型有异质性,可表现为AGS或遗传性对称性色素异常症。     

Aicardi-Goutières综合征一家系并文献复习北大核心CSCD

目的 探讨一个Aicardi-Goutières综合征（AGS）家系的临床及影像学特点,并检测其致病基因的突变情况,结合文献总结AGS综合征的临床及基因突变特点.方法 收集2013年1月于北京大学第一医院儿科神经病房住院的一个AGS家系的临床资料,采用DNA直接测序对致病基因行突变检测.在Pubmed、OVID、CNKI、万方等医学文献数据库,采用“Aicardi-Goutières syndrome”或“Aicardi-Goutières综合征”为关键词检素1984年1月至2014年7月文献.并对已报道的252例AGS病例进行复习.结果 （1）临床特点：先证者男,6岁7个月,自幼智力运动发育落后,1岁时发现患儿姿势异常表现为四肢扭转,运动时明显.阳性体征：四肢末端较多冻疮,头围小（47.5 cm）,活动时有明显肌张力不全.头颅CT示多发钙化,基底节为著;头颅MRI示脑白质长T1W、长T2W信号,颞叶皮质下白质可见囊性变.先证者妹妹发育正常,面部及四肢末梢可见冻疮,头颅CT示多发钙化,基底节为主.（2）基因突变分析：先证者及其妹妹TREX1发现两个突变,c.294_295insA为未报道的无义突变,c.868_885del为已知致病突变.（3）文献总结：AGS常见的表现包括发育落后[92％（231/252）],肌张力不全[75％（189/252）],小头畸形[63％（159/252）]、冻疮[42％ （106/252）]、基底节钙化[100％（252/252）]、脑萎缩[88％ （222/252）]及脑白质病变[86％（217/252）].在AGS6个致病基因中以TREX1[38％ （96/252）]和RNASEH2B[23％（58/252）]突变较为常见.结论 明确了该AGS家系中的致病基因为TREX1基因突变,为该家庭进行准确的遗传咨询提供了可能.c.294_295insA为未报道的无义突变.     

TREX1基因变异致Aicardi-Goutières综合征1例报告

目的 总结TREX 1基因变异致Aicardi-Goutières综合征(AGS)的临床及基因特征.方法 回顾分析1例新生儿期起病的AGS综合征患儿的临床资料.结果 女性患儿于生后第2天起发热、喂养困难、呼吸困难;特殊面容,头型尖、头围小(30 cm)、眼距宽、眼裂窄、鼻梁低平、上唇短小、短下颌,四肢肌张力低,原始反射...     

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Alagille综合征是具有表型特征的慢性胆汁淤积的最常见原因,是一种累及多系统的显性遗传性疾病[1].该综合征在1969年由Alagille等首次报道,并在1975年得到进一步阐述[2].     

IFIH1基因突变致Aicardi⁃Goutières综合征7型1例并文献复习

目的 报道1例Aicardi-Goutières综合征(AGS)7型患儿的临床特点,总结国外既往报道病例特点.方法 回顾分析1例AGS7型患儿的临床表现、Ⅰ型干扰素刺激基因表达和全外显子(WES)测序结果.检索PubMed数据库、万方数据库及中国知网数据库中IFIH1或MDA5基因突变导致AGS7的病例,总结临床特征和...     

Les dyspraxies : points de repères

Despite its frequency, little is known about dyspraxia. Dyspraxia, which represents disorders in development and learning movements, within the context of a deficiency in the management of spatial information (in children whose verbal intelligence is spared), is often a severe handicap at school and in social life. Dyspraxia must be distinguished from “common” difficulties of unmotivated children at school, with which it is often confused. Hence, the diagnosis must correspond to rigorous methodology. And one should avoid proposing endless training for the deficient action (writing, getting dressed…); indeed such strategies only lead to short-term ‘pseudo’ progress, without any long term efficacy on the educational success of these intelligent children. To the contrary, the child should be rapidly oriented in two therapeutic directions: (1) a battle between the “double-task” effect stemming from the graphical and spatial difficulties; (2) the use of palliatives (including computing). In conditions of early diagnosis (at 4–8/9 years of age) and well-coordinated management with the school, the prognosis would be excellent in terms of schooling, choice of a profession and social insertion. If not, or if (as is the case in almost a third of cases) dyspraxia is not isolated (associated with dyslexia, hyperactivity, attentional deficit and psychotic traits), the child should be oriented towards a specialised classroom and care.     

Les maisons des adolescents : une vieille histoire ? Les MDA vues comme modèles de nos manières de considérer les adolescents

Since the period of adolescence was first identified in the mid nineteenth century, its evolution has, unsurprisingly, lead to the creation of “houses” to accommodate adolescents. Today, each department of France is developing its own respective system. The diversity originates from their founders’ unique perspective and the ideas of how adolescents should be treated. The stake of these houses relies on putting them back into perspective by looking at the history of adolescence and its precursors. In fact, by studying, on the one hand, the confluence of our representations regarding the period of adolescence and, on the other hand, the evolution of our institutions, it is possible to report issues with the adolescent houses of today and deduce what they will be like tomorrow.     

Bronchiolite et prise alimentaire des dernières 24 h : un outil de dépistage de l’hypoxie

BackgroundHypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24 h (bottle and spoon feeding), as a percentage of usual intake (24 h FI), as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs.MethodsIn this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea + dyspnea + cough + expiratory sounds). Infants with risk factors (history of prematurity, chronic heart or lung disorders), breast-fed infants, and infants having previously been treated for bronchial disorders were excluded. The 24 h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO₂) was recorded. Hypoxia was noted if SpO₂ was below 95% and verified.Results24 h FI greater or equal to 50% was associated with a 96% likelihood of SpO₂ greater or equal to 95% [95% CI, 91–99%]. In univariate analysis, 24 h FI less than 50% had the highest odds ratio (13.8) for SpO₂ less than 95%, compared to other 24 h FI values and other clinical signs, as well as providing one of the best compromises between specificity (90%) and sensitivity (60%) for identifying infants with hypoxia. In multivariate analysis with adjustment for age, SpO₂ less than 95% was related to the presence of intercostal retractions (OR = 9.1 [95% CI, 2.4–33.8%]) and 24 h FI less than 50% (OR = 10.9 [95% CI, 3.0–39.1%]). Hospitalization (17 infants) was strongly related to younger age, 24 h FI and intercostal retractions.ConclusionIn practice, the measure of 24 h FI may be useful in identifying hypoxia and deserves further study.     

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??Abstract?? Objective To analyze ALDH3A2 mutation in four Chinese patients with Sjögren-Larsson syndrome ??SLS??. Methods Four patients were clinically diagnosed with SLS. Respectively take 3 ml of peripheral blood. All 11 exons and exon-intron boundaries of ALDH3A2 gene were amplified by polymerase chain reaction ??PCR?? and directly sequenced for genomic DNA. Results 1. All four patients had congenital ichthyosis?? mental retardation??and spastic diplegia or tetraplegia. Patient 1 had a compound heterozygote??c.1157A??G inherited from her father?? IVS5-1del G inherited from her mother. Both her parents had normal phenotype. Patient 2 and Patient 3 were siblings?? they were both homozygotes??a A-to-G transition at nucleotide 1157 in exon 8. The heterozygosity was demonstrated in their mother. Both her parents had normal phenotype. Conclusion Two different mutations were examined in these 4 Chinese patients?? and the SLS cases were confirmed by ALDH3A2 mutation analysis.     

Aicardi–Goutières syndrome presenting with haematemesis in infancy

Aicardi–Goutières syndrome is a genetic childhood encephalopathy characterized by basal ganglia calcification, chronic cerebrospinal lymphocytosis and elevated cerebrospinal fluid interferon-alpha, mimicking acquired congenital viral infections. As more is discovered about the pathogenesis of Aicardi–Goutières, it is becoming evident that a dysfunction of the immune system is likely to be responsible for the disease phenotype. We describe a previously healthy 2-month-old female infant who presented with haematemesis and seizures and was subsequently diagnosed with Aicardi–Goutières syndrome. To our knowledge, this is the first documented case of Aicardi–Goutières syndrome presenting with haematemesis. The gastrointestinal tract is an area of high cell loss, revealing early signs of systemic inflammation and we postulate that a systemic proinflammatory milieu occurs in Aicardi–Goutières syndrome.
Conclusion: Aicardi–Goutières syndrome can present with haematemesis, adding to the growing evidence that the Aicardi–Goutières syndrome spectrum encompasses an immune-mediated multisystem involvement. Gastrointestinal inflammation should also be considered in these patients and treated appropriately.     

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??To perform mutation analysis in a pseudoachondroplasia ??PSACH?? family. Methods??Mutation screening was carried out by DNA-PCR and direct sequencing the exons 8 to 19 of COMP gene. Results??A c.815C > T substitution was identified in exon 8 of COMP gene in the proband and his affected father and brother. Conclusion??The disease in the family is caused by mutation of COMP gene.     

Novel <Emphasis Type="Italic">OCRL1</Emphasis> gene mutations in six Chinese families with Lowe syndrome

Background

Lowe syndrome, an X-linked, inheritable disease with clinical symptoms of congenital cataracts, incomplete Fanconi syndrome, and mental retardation, has an approximate incidence of 1 in 500 000. Nearly 200 OCRL mutations related to Lowe syndrome have been found worldwide, with only ten mutations among the Chinese population. Since more mutations may exist in Chinese patients, we sequenced and analyzed the OCRL genes of six children with Lowe syndrome in a medical center in China.

Methods

Peripheral blood was collected from six children with Lowe syndrome and their relatives, and ten healthy adults. Genomic DNA was extracted from the blood and applied to amplify the twenty-four exons and flanking introns of the OCRL gene. The mutations were identified by sequencing.

Results

Five mutations (c.1528C>T, c.2187insG, c.1366C>T, c.1499G>A, and c.2581G>A) of the OCRL gene were found in five families; c.2187insG and c.1366C>T were novel mutations. None of the five mutations were detected in 20 normal chromosomes. No mutation was found in the sixth family.

Conclusion

Two novel mutations of the OCRL gene, c.2187insG and c.1366C>T, were found in Chinese patients with Lowe syndrome, which will provide new clues for the etiology of Lowe syndrome and could be beneficial to genetic diagnosis of the condition.

     

An Egyptian family with H syndrome due to a novel mutation in SLC29A3 illustrating overlapping features with pigmented hypertrichotic dermatosis with insulin‐dependent diabetes and Faisalabad histiocytosis

The SLC29A3 gene, encoding hENT3, a member of the equilibrative nucleoside transporter family, has recently been found mutated in Faisalabad histiocytosis, pigmented hypertrichotic dermatosis with insulin‐dependent diabetes, familial sinus histiocytosis with massive lymphadenopathy (SHML), and H syndromes. We here report clinical and genetic findings of an Egyptian family with H syndrome. We describe two siblings, a 19‐yr old girl and a 15‐yr old boy, of consanguineous parents. From 5 yr of age, the girl developed bilateral flexion deformity of interphalengeal joints and insulin‐dependent diabetes mellitus. At age 7 yr, prominent hyperpigmented patches appeared on the skin at lower limbs, genitalia, and trunk. On clinical examination, she had hepatosplenomegaly, generalized lymphadenopathy, left ventricular hypertrophy, sensorineural hearing loss, hypogonadism, short stature, and characteristic dysmorphic features. Her brother had fixed flexion contractures of the feet, profound sensorineural hearing loss, characteristic dysmorphic features, but no diabetes. DNA sequence analysis revealed a homozygous mutation (c.300+1G>C) in SLC29A3 in both siblings. The phenotype and genotype of the siblings were compatible with that of the H syndrome, although the features were overlapping with those found in pigmented hypertrichotic dermatosis with insulin‐dependent diabetes, familial SHML, and Faisalabad histiocytosis, indicating that these four syndromes may be regarded as one disease with varying phenotypic features. A new, common name for these conditions is warranted.     

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??Objective??To improve the level of diagnosis and treatment of children with Kimura’s disease complicated with nephrotic syndrome. Methods??In order to understand the current pathogenesis??diagnosis and treatment of children with Kimura’s disease complicated with nephrotic syndrome??we reviewed 3 cases of Kimura’s disease in our department from 2011 to 2015??and studied the related literature at home and abroad at the same time. Results??Kimura’s disease is a rare chronic immune inflammatory disease which mainly damaged lymph nodes??soft tissue and salivary glands. It mostly occurs in Asian people between the age of 28 and 32??especially male. At present??the cause of the disease and its pathogenesis is still unclear. Histopathology is the only way to diagnose Kimura’s disease. As the golden standard of kidney disease diagnosis??renal biopsy is a big help for the diagnosis and treatment of renal damage of Kimura’s disease. Current treatments mainly depend on medication??and generally hormone combined immune inhibitors are used. Conclusion??Kimura’s disease is a chronic disease??which is a benign lesion but easy to recur. There usually is no malignant change.     

A novel missense mutation in the EVC gene underlies Ellis‐van Creveld syndrome in a Pakistani family

Background: Ellis‐van Creveld (EVC) syndrome is a rare autosomal recessive disorder characterized by skeletal, ectodermal and cardiac defects. This syndrome is caused by mutations in EVC and EVC2 genes, which are separated by 2.6 kb of genomic sequence on chromosome 4p16. Methods: In the present study we ascertained a four‐generation pedigree of Pakistani origin with features of EVC. Linkage was searched by genotyping microsatellite markers linked to chromosome 4p16. Affected individuals showed homozygosity to the microsatellite markers tightly linked to EVC and EVC2 genes on chromosome 4p16. It was then subjected to direct sequencing of the EVC and EVC2 genes. Results: Mutation analysis of the EVC and EVC2 genes identified a novel missense change (c.617G>A; p.S206N) in the EVC gene. Conclusions: We herein report on the first family from Pakistan with a large number of individuals affected by EVC. DNA sequence analysis led to the identification of the fifth missense mutation in the EVC gene.     

Apert 综合征 1 例临床特征与基因类型分析

目的分析Apert综合征(AS)临床特征与基因类型。方法回顾1例AS患儿的临床资料及患儿和其父亲FGFR2基因测序结果,并复习相关文献。结果男性患儿,1岁1个月,扁头,突眼,眼距宽,耳位低,下颌小,高腭弓,无腭裂,双手五指并指并挛缩,双足五趾并趾。FGFR2基因外显子7 c.758CG,p.P253R杂合变异,父亲未检测到相关基因突变,支持Apert综合征诊断。文献检索到AS个案24例,22例明显颅面部畸形,1例轻微畸形,1例无畸形;均有手足并指/趾畸形。基因类型为S252W 13例,P253R 3例,Alu元件插入3例,基因缺失2例,杂合突变2例,序列变异1例。结论 AS患儿颅面部畸形及手足并指/趾明显,FGFR2基因以S252W、P253R突变为主。     

Wiskott-Aldrich 综合征1 例临床及基因分析

目的探讨Wiskott-Aldrich综合征(WAS)的WAS基因突变的特点。方法回顾分析1例WAS患儿的临床资料,以及利用PCR测序方法检测WAS基因全部外显子及侧翼序列。结果 5个月男性患儿,发现血小板减少入院,既往湿疹时间长且反复感染;CD8+及CD4+T淋巴细胞升高,CD 19+B淋巴细胞正常;骨髓细胞学提示巨核细胞成熟障碍。WAS基因检测发现存在C.880 AG(p.Ile294Val)突变,患儿父母均未见突变。利用Polyphen2软件及SIFT软件预测该位点为致病性突变,不同物种间序列保守性分析发现该位点保守;结构预测分析发现该位点突变可能会影响正常的蛋白结构,该突变国内外未见报道。结论基因检测可早期诊断WAS,新发现C.880 AG(p.Ile294Val)突变。