少汗型外胚层发育不良一家系EDA基因突变分析

目的分析X连锁少汗型外胚层发育不良家系的基因变异及遗传咨询。方法采用二代测序法查找先证者致病基因及其突变位点,Sanger测序验证。根据基因诊断结果对先证者母亲第2胎进行产前分子诊断。结果先证者男性,出生10天,因发热、特殊面容就诊。经基因检测发现EDA基因c.682_683delCCinsA杂合突变,母亲具有相同突变。第2胎经羊水穿刺,基因检测未发生以上突变。结论基因检测有助于明确少汗型外胚层发育不良家系患儿的遗传病因,在此基础上可对患儿家系进行遗传咨询和产前基因诊断。     

少汗性外胚层发育不良一家二例

先证者男 ,6岁。因“毛发稀疏 ,少汗 6年”来我科就诊。患儿出生时毛发稀少 ,从生后 4d起开始反复出现不明原因发热 ,一般为低热 ,但最高可至 39～ 40℃。夏季烦躁不安 ,全身无汗。 4岁后在炎热及剧烈活动后两侧腋窝少量出汗 ,其他部位仍无汗 ,必须借助冷水浴降温。反复发热至 5岁时有所缓解 ,但毛发稀少及少汗症状无好转。 6岁时方萌出一颗乳磨牙。智力发育与同龄人相当。体检 :身高 1 1 7cm ,体重 1 8kg ,营养中等。特殊面容 ,额部隆起 ,鼻梁塌陷如马鞍形 ,上下唇厚。皮肤干燥见细小皱纹 ,口周和眼周有放射沟 ,颊部毛细血管扩张。头发稀疏…     

无汗/少汗性外胚层发育不良4例报告

<正>例1:男,10个月,因间断发热9月余伴咳嗽2周入院。系第2胎第2产,足月顺产。生后即发现全身松软,肌张力低下。新生儿期后出现间断发热,体温波动在正常至38℃之间,进入夏季后发热更明显,最高可至39℃,可通过物理降温或自行降至正常,口服退热药基本不出汗。其兄体健。父母体健,     

1个有汗性外胚层发育不良大家系的基因研究

目的 探讨有汗性外胚层发育不良 （HED）的临床特点和分子机制。方法 对1例HED先证者进行其家系5代91人的临床及基因特点研究。抽取家系中7名患者及3名正常对照进行GJB6基因检测。结果 家系5代91人中,HED患者17例,表现为不同程度的指 （趾）甲发育不良、毛发或体毛稀少甚至缺如;家系中男性患者毛发稀少程度重于女性;随着代数增加,指 （趾）甲损害渐减轻。系谱中每一代均有发病者,患者的父母中必有一人发病;男女都可患病;遗传方式为常染色体显性遗传。家系中所有患者的GJB6基因均存在一个杂合错义突变31G→A,家系中无HED临床表现的未检测到此突变。结论 HED为常染色体显性遗传性疾病,以指 （趾）甲发育不良、掌跖角化过度、毛发或体毛稀少甚至缺如为临床特点;男性毛发稀少重于女性;且随着代数的增加,指 （趾）甲损害逐渐减轻。GJB6基因错义突变 （31G→A）是HED的分子机制之一。     

Alagille综合征患儿1例临床和遗传学分析:一个包含JAG1基因的染色体新中间缺失的识别

Alagille综合征(ALGS)是一种常染色体显性遗传病,可累及肝脏、心脏、骨骼、眼睛、肾脏、颜面等多个系统。本文报道1例ALGS患儿的临床和遗传学特征。患儿为3个月10d男婴,因发现皮肤、巩膜黄染3个月就诊。体格检查示:宽额头,小下颌;胸骨左缘第2、3肋间可闻及3~4/6级收缩期杂音;腹部膨隆,肝右肋下3cm可触及,质地中等。生化结果示肝功能明显异常,胆红素升高,且以结合胆红素升高为主,伴总胆汁酸和γ-谷氨酰转肽酶显著升高。心脏彩超示房间隔缺损、肺动脉狭窄。二代测序发现该患儿JAG1基因整体杂合缺失,而染色体微阵列分析在患儿20号染色体p12.3p12.2处检出约3.0Mb缺失,该范围包含ALGS致病基因JAG1。该患儿具备特殊面容、心脏畸形和胆汁淤积等临床表现,结合遗传学分析结果,诊断ALGS明确。确诊后给予对症支持治疗,现已随访至生后11个月,胆红素较治疗前明显下降,但总胆汁酸和γ-谷氨酰转肽酶等指标仍明显升高,其远期预后仍有待随访观察。本研究扩展了JAG1基因突变谱,同时为患儿诊断、治疗及家系遗传咨询和产前诊断提供了实验室依据。     

NROB1基因错义突变致新生儿先天性肾上腺发育不良1例报告

目的探讨X连锁先天性肾上腺发育不良(AHC)的临床特点及诊断。方法回顾性分析1例AHC患儿的临床资料及基因检测结果,并复习相关文献。结果 2个月男性患儿,生后即出现体质量不增伴呕吐,伴有肾上腺功能不全失盐危象。基因检测发现NROB1基因错义突变,确诊为X-连锁先天性肾上腺发育不良。结论 X连锁先天性肾上腺发育不良是一种罕见病,诊断主要是通过临床表现、实验室检测及NROB1基因检测。     

BBS1基因新突变导致Bardet-Biedl综合征的遗传学分析及产前诊断

<正>1 病例资料先证者,孕23+4周胎儿。孕妇,30岁,第3次妊娠,孕17+3周在外院行唐氏筛查,21三体、18三体和开放性神经管畸形(ONTD)筛查低风险,孕22+5周在外院行超声产前筛查,宫内妊娠,单活胎,胎儿左手异常(考虑多指畸形)、胎儿双肾增大并实质回声弥漫性增强(考虑多囊肾),转诊贵州医科大学附属医院(我院)产前诊断中心。本次妊娠自然受孕,无妊娠合并症、无放射性物质接触史、无服用药物史。其丈夫31岁,体健。否认近亲结婚、疾     

CHD8基因新发突变的孤独症谱系障碍1例报道并文献复习

目的提高对孤独症谱系障碍(ASD)CHD8基因突变患儿临床表型和基因型的认识。方法回顾性分析1例存在CHD8基因突变的ASD患儿的临床资料,并文献复习。结果 1男,3岁3月龄,头围55.0 cm(4 s),身高107.0 cm(2 s),体重23.5 kg(2 s)。有典型的ASD表现,运动明显落后,有慢性便秘史。2提取患儿及其父母静脉血DNA,以二代高通量测序技术对4 813个临床相关基因的外显子区进行测序,共检测到变异8 982个,经筛选流程筛选ASD相关的EHMT1、PCDH9、NLGN4X的错义突变,CHD8的无义突变(c.307CT,p.Gln103*)有致病可能。Sanger测序显示患儿EHMT1、PCDH9的突变来源于父亲,NLGN4X的突变来源于母亲,患儿父母未发现CHD8的突变。3目前国外共报道了CHD8基因与神经发育障碍有关的15个重要突变;CHD8基因突变患者的临床表型包括ASD表现(87%)、身材高大(86%)、大头畸形(80%)、慢性便秘或间歇性腹泻(80%)、运动落后(67%)和睡眠异常(67%)等,本文病例临床表型与文献报道较为一致。结论 CHD8基因是ASD重要的易感基因;ASD患儿合并大头畸形、生长过快,且有慢性便秘或间歇性腹泻时应考虑CHD8基因突变可能,可行基因检测协助诊断。     

粕D2基因双位点突变导致Blau综合征的家系分析北大核心CSCD

目的通过对一疑似Blau综合征（Bs）的中国家系进行NOD2基因分析,研究中国患者的基因突变类型和临床特点。方法研究对象为疑似Bs患儿及其家属,共9例。其中男4例,女5例。患儿及其父母进行Sanger测序和医学外显子测序,其余人员仅进行Sanger测序;对于新发现错义突变,在线预测其致病性;结合基因型与Bs患者的临床资料,为Bs的诊断提供临床依据。结果1．序列分析结果显示,先证者NOD2基因4号外显子的2处位点同时发生错义突变,一处为已知突变：c．2006A〉G,P．I-1669R,另一处为新发突变：c．1981G〉C,P．A661P。2．经家系验证分析,先证者之父和祖母在这2个位点具有同样的杂合变异,先证者之母和祖父该位点无变异。3．先证者具有皮疹、虹膜睫状体炎和关节炎三联征症状,无发热,c反应蛋白（CRP）正常。结论家系中NOD2基因A661P和H669R双突变引起BS,突变由祖母经父亲传递给先证者;A661P是个新发现的突变位点;先证者无反复发热,CRP不升高,该临床表现有可能作为本病区分于其他白发炎症性疾病的鉴别标准。     

A new mutation in EDA gene in X-linked hypohidrotic ectodermal dysplasia associated with keratoconus

Hypohidrotic ectodermal dysplasia (HED) was first described in 1848 by Thurnam. HED belongs to ectodermal dysplasias (EDs), which are developmental impairments of ectodermal-derived tissues. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of the EDs and consists in abnormal development of teeth, hair, and eccrine sweat glands. XLHED is determined by mutations in the ED1 gene, which is responsible for the coding of ectodysplasin-A(EDA-A), a protein that regulates ectodermal appendage formation. In the present study we found both in our proband and in the mother the same missense mutation in exon 9 (c.957 C>A), which resulted in an aminoacid change at position 319 (Ser319Arg). This latter anomaly might alter the charges in the TNF domain of EDA-A, affecting the stability of the protein and therefore the interaction with its receptor. The male propositus presented classical manifestations of HED except for keratoconus (KC) and, to the best of our knowledge, this association has not been previously described. The identification of this new mutation may contribute to evaluating the genotype/phenotype correlations. Finally, this report can give useful information about the genetic basis of KC and HED. Future studies will allow us to understand if a genetic bond exists between them.     

A novel NEMO gene mutation causing osteopetrosis, lymphoedema, hypohidrotic ectodermal dysplasia and immunodeficiency (OL-HED-ID)

Genetic conditions are increasingly recognised as a cause of multisystem diseases in children. We report a 6-year-old boy with hypohidrotic ectodermal dysplasia, immunodeficiency, osteopetrosis and lymphoedema, associated with a novel mutation in the NF–κβ essential modulator (NEMO) gene. He is the longest surviving of three reported boys with these clinical features. Hypohidrotic ectodermal dysplasia, a congenital disorder of teeth, hair and eccrine sweat glands is most commonly inherited as an X-linked recessive trait. Associated immunodeficiency (HED-ID) may give rise to serious infections in early life. Mutations in the NEMO gene give rise to a heterogeneous group of disorders, including the X-linked dominant disorder incontinentia pigmenti. This is characterised by typical skin changes leading to linear pigmentary change and variable associated features; in males, prenatal death usually occurs. Our patient, like one if the previous cases and all of their mothers, demonstrates features of incontinentia pigmenti.     

POLG 基因变异致线粒体病一家系分析

目的分析POLG基因变异致线粒体病的临床表型及基因变异。方法回顾分析于2019年5月就诊,并经采集外周血DNA进行医学外显子、外显子-内含子交界区靶向二代测序和一代验证,1个确诊为POLG基因变异致线粒体病家系的临床资料。结果先证者,男,10岁,与其同卵双胎哥哥均有相同的体征,深感觉受损、腱反射消失、肌肉可疑萎缩。先证者3个兄姐先后于1岁多夭折。提取患儿及其父母的外周血,先证者及同卵双胎哥哥POLG基因均存在G.2558A(p.R853Q)、c.2890T(p.R964C)复合杂合变异,分别来源于患儿父母亲。结论 POLG基因复合杂合变异线粒体病家系成员有不同的表型;POLG相关疾病,即使同种基因变异,其临床异质性也较大。     

Clinical aspects of X-linked hypohidrotic ectodermal dysplasia.

Boys with X-linked hypohidrotic ectodermal dysplasia and their families were studied. Many suffered severe illness in early childhood and nearly 30% died; many had feeding problems, severe fever, atopic disease, and recurrent respiratory infections. Some infants failed to thrive. We found no consistent common endocrine or immunological abnormality, although, most had abnormal immunoglobulin production. This may be related to the abnormal mucosa of the gastrointestinal and respiratory tracts which exacerbates the chronic obstructive airways disease found later in life in those who smoke. Mental handicap was not a feature, although convulsions sometimes occurred during fever. Early diagnosis is important to avoid attacks of severe fever and so that rational management may be planned for other problems that arise. Dental advice should be sought before school age and genetic counselling may also be required. Many female carriers may be recognised at clinical examination: their affected sons can then be diagnosed more readily.     

新复合杂合突变致婴儿型低磷酸酯酶症1例及其家系分析

该文对1例婴儿型低磷酸酯酶症(HPP)患儿及其家系进行临床特点分析及碱性磷酸酯酶基因(ALPL)检测。先证者,男,5个月,多发骨骼畸形:胸骨凹陷、双侧桡骨弯曲畸形、双膝外翻畸形,伴喂养困难、体重下降、发育迟滞、反复肺炎并呼衰,血碱性磷酸酶显著降低。患儿父母、姐姐、叔父、姨母(其他家系成员未能配合)中除父母及姨母的碱性磷酸酶略低,姨母可见脊柱侧弯畸形,余均无临床表型及实验室异常。患者ALPL基因检测到来源于母亲的c.228delG突变及来源于父亲的c.407GA复合杂合突变,其姨母携带c.228delG突变。c.407GA突变为已报道的HPP致病突变,c.228delG为新的致病性突变。低磷酸酯酶症是由ALPL基因突变所致,ALPL基因检测是有效的诊断方法。该研究拓展了ALPL基因突变谱,为HPP的基因诊断提供了理论依据。