X连锁少汗性外胚叶发育不良家系基因突变检测

目的:检测1例3月龄少汗性外胚叶发育不良男性患儿及其家族成员少汗性外胚叶发育不良(ED1)基因的突变.方法:提取家系成员白细胞中的DNA,设计引物特异扩增ED1基因的外显子及其侧翼区域并测序,与正常人的测序结果进行比较.结果:患儿ED1基因第466位碱基由胞嘧啶变为胸腺嘧啶,使翻译产物中相应的氨基酸由精氨酸变为半胱氨酸,即R156C.先证者母亲为杂合子,父亲未检测到突变.结论:R156C导致了X连锁少汗性外胚叶发育不良在该家系中的传递.     

X连锁少汗性外胚叶发育不良一家系ED1基因突变检测研究

目的:研究X连锁少汗性外胚叶发育不良一家系患者的临床表现及其致病原因.方法:在患者家系调查的基础上,收集家系中患者和正常人的血样,并采集正常对照血样100份,采取聚合酶链反应技术对ED1基因进行扩增,并对其产物进行测序.结果:该家系中所有的患者均表现为汗腺缺乏或减少,毛发稀少,全部或部分牙齿缺损.ED1基因第9号外显子存在1个22个碱基缺失突变.结论:该家系发病是由ED1基因突变所致,其发病的基因型和表型之间的关系有待于进一步研究.     

有汗性外胚叶发育不良一家系致病基因突变筛查

目的:寻找有汗性外胚叶发育不良家系GJB6、GJB2和CTSC突变基因.方法:抽提外周血DNA,PCR扩增GJB6、GJB2和CTSC基因编码区的所有外显子,扩增产物纯化后直接双向测序,并与基因组序列进行比对分析,查找有无突变.结果:候选基因编码区所有外显子均未发现突变.结论:GJB6、GJB2和CTSC基因编码区序列与本研究中有汗性外胚叶发育不良家系发病无关,致病基因待进一步研究.     

有汗性外胚叶发育不良2例

例1，女，25岁，出生后全身毛发稀少，且易脱落，尤以头发最为明显，同时伴有眉毛的缺失，双手指甲颜色及形状异常，出汗正常。父母非近亲结婚，父亲病故（病因不详），同母异父兄妹均无脱发症状。     

少汗性外胚叶发育不良1例

患者男，20岁，因全身毛发稀少，怕热无汗20年于2002年10月12日来我所就诊，患者于出生时头发及眉毛较少，且随时间推移毛发逐渐减少，17岁时，眉毛，腋毛基本脱失，未曾长过胡须。20年来，患者非常怕热，全身未曾出过汗，经常不明原因发热，夏季尤甚，幼时出牙迟，乳牙极少，恒牙稀，吐词不清，其     

有汗性外胚叶发育不良1例

临床资料患儿,女,3岁。主因秃发3年伴掌跖红斑角化脱屑1年,于2008年11月来我科就诊。患者出生时头皮无毛发生长,视力进行性下降,6月龄时于当地医院诊断为"先天性白内瞕",行白内瞕晶状体摘除术。1年前双手指、掌跖部开始出现红斑、脱屑,伴轻度疼痛,皮疹呈进行性加重。患儿发病后皮肤出汗正常     

无汗性外胚叶发育不良1例

患者男,23岁,因怕热无汗,全身毛发稀疏,牙齿发育不全23年就诊。皮肤科情况头发稀疏、细、短而干燥,眉毛稀少,外2/3缺如。睫毛正常,胡须、阴毛、腋毛及四肢毳毛缺如。额轮突出,颧骨高且宽而下半脸狭小。鼻尖小且上翘,鼻孔则大而显著。颊部毛细血管扩张,且有小丘疹如皮脂腺瘤。嘴唇厚,上唇尤为突出。牙齿部分缺失。仅有4颗犬齿,呈锥状尖牙,牙龈萎缩。组织病理表皮薄而扁平。诊断为无汗性外胚叶发育不良。     

有汗性外胚叶发育不良1例

患儿女,13岁.全身毛发脱落、稀少12年.患者出生时头发稀疏,指(趾)甲板薄软.半年后头发及眉毛呈渐进性脱落,同时全身毳毛也渐稀少.随着年龄增长头皮间断有少量毳毛长出,但头部新长出的毳毛很快脱落,不能长成正常头发.     

有汗性外胚叶发育不良1例

患者男,25岁.因普秃25年,掌跖角化、甲板异常23年,于2006年4月3日来我院就诊.     

X连锁少汗性外胚层发育不良一家系EDA基因的突变

目的检测一X连锁少汗性外胚层发育不良家系的EDA基因突变。方法收集患者及其父母资料,提取外周血DNA,采用PCR扩增EDA基因编码区的全部外显子及其侧翼序列,PCR产物测序,明确突变位点。以50例无关健康人作对照。结果该家系患者第7号外显子第895位鸟嘌呤G突变成腺嘌呤A,使EDA编码的蛋白第299位氨基酸密码子GGC变成AGC,导致正常的甘氨酸被丝氨酸所代替。其母亲在相同位置的碱基出现G-A双峰,显示为杂合性携带者,其父亲及50例无关健康对照未见此改变。结论G299S可能是导致该X性连锁少汗性外胚层发育不良家系临床表型的原因。     

Novel mutation of EDA causes new asymmetrical X‐linked hypohidrotic ectodermal dysplasia phenotypes in a female

Hypohidrotic ectodermal dysplasia (HED) is a rare hereditary disorder that affects tissues derived from the ectoderm including hair, teeth and sweat glands. EDA is the major causative gene of HED. This study recruited a Chinese family with HED, including a male proband and his mother with a fetus. The proband had typical clinical features of HED and the mother had identical but milder features. Interestingly, some phenotypes of the mother appeared asymmetrically between the right and left side of the body that were not reported in previous studies. Targeted sequencing was performed in the proband and a novel frame‐shift mutation (NM_001399.4: c.381_382delinsG, p.Q128Rfs*9) in EDA was found. Sanger sequencing validated the mutation and identified the same mutation in the mother. Our study expands the clinical and genetic spectrum of EDA‐related disorders and reports new asymmetrical phenotypes in a female.     

A case of hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a rare, hereditary, congenital disease that affects several ectodermal structures. It is characterised by the following: anhidrosis or hypohidrosis, dental abnormalities, hypotrichosis, and a characteristic facies. The face shows prominent frontal bosses, supraorbital ridges and depressed bridges. We experienced a case of hypohidrotic ectodermal dysplasia in a 43-year-old male who had four characteristic features. A skin biopsy from the palm showed a total absence of the eccrine glands. The diagnosis was made on the basis of clinical features and skin biopsy findings.     

Molecular genetic analysis of consanguineous Pakistani families with autosomal recessive hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia is an inherited disorder characterized by defective development of teeth, hairs and sweat glands. X-linked hypohidrotic ectodermal dysplasia is caused by mutations in the EDA gene, and autosomal forms of hypohidrotic ectodermal dysplasia are caused by mutations in either the EDAR or the EDARADD genes. To study the molecular genetic cause of autosomal recessive hypohidrotic ectodermal dysplasia in three consanguineous Pakistani families (A, B and C), genotyping of 13 individuals was carried out by using polymorphic microsatellite markers that are closely linked to the EDAR gene on chromosome 2q11-q13 and the EDARADD gene on chromosome 1q42.2-q43. The results revealed linkage in the three families to the EDAR locus. Sequence analysis of the coding exons and splice junctions of the EDAR gene revealed two mutations: a novel non-sense mutation (p.E124X) in the probands of families A and B and a missense mutation (p.G382S) in the proband of family C. In addition, two synonymous single-nucleotide polymorphisms were also identified. The finding of mutations in Pakistani families extends the body of evidence that supports the importance of EDAR for the development of hypohidrotic ectodermal dysplasia.     

Novel mutations in the EDAR gene in two Pakistani consanguineous families with autosomal recessive hypohidrotic ectodermal dysplasia

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a human heritable disorder characterized by sparse hair, a lack of sweat glands and malformation of teeth. There are X-linked, autosomal recessive and autosomal dominant forms of this disorder. Mutations in the EDA gene cause X-linked HED and mutations in either the EDAR or the EDARADD genes cause autosomal forms of HED. OBJECTIVES: To identify pathogenic mutations in two consanguineous Pakistani families (A and B) with 11 affected individuals demonstrating the autosomal recessive form of HED. METHODS: Genotyping of 17 members of the two families, including eight affected and nine unaffected individuals, was carried out by using polymorphic markers D2S293, D2S1893 and D2S1891, which are closely linked to the EDAR gene on chromosome 2q11-q13. To screen for mutations in the EDAR gene, all of its exons and splice junctions were polymerase chain reaction amplified from genomic DNA and sequenced directly in an ABI Prism 310 automated sequencer. RESULTS: Genotyping results showed linkage in both the Pakistani families to the EDAR locus. Sequence analysis of the EDAR gene identified two novel mutations in the families: a missense mutation (G382S) in family A and a 4-bp deletion (718delAAAG) in family B. CONCLUSIONS: We describe novel mutations in the EDAR gene in two Pakistani families affected with the autosomal recessive form of HED. Our findings extend the body of evidence that supports the importance of the ectodysplasin A1 isoform receptor, a member of the tumour necrosis factor receptor family, in the development of ectodermal appendages.     

Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases

Background Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the eccrine sweat glands, hair and teeth. The X‐linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal dominant and recessive forms occasionally occur and result from mutations in at least two other genes: EDAR and EDARADD. EDARADD interacts with the TAB2/TRAF6/TAK1 complex, which is necessary for NF‐κB activation by EDAR. Objectives To determine frequency of EDARADD, TRAF6, TAB2 and TAK1 mutations in HED. Materials and methods We have screened 28 familial or sporadic HED cases with no mutations in the EDA and EDAR genes for EDARADD, TRAF6, TAB2 and TAK1 mutations. Results We identified one EDARADD 6‐bp homozygous in‐frame deletion (c.402‐407del, p.Thr135‐Val136del) in a patient born to consanguineous parents. Functional studies showed that the p.Thr135‐Val136del impaired the EDAR–EDARADD interaction and then severely inhibited NF‐κB activity. In the remaining 27 patients, we failed to find causative mutations in EDARADD, or in TRAF6, TAB2 or TAK1. Conclusions Our study demonstrates that EDARADD mutations are not a frequent cause of HED, while mutations in TRAF6, TAB2 and TAK1 may not be implicated in this disease.     

有汗性外胚层发育不良一家系基因突变

目的 探讨有汗性外胚层发育不良家系的基因突变及突变类型,为建立本病的基因诊断与遗传咨询提供依据。方法 PCR及Sanger测序技术对有汗性外胚层发育不良家系先证者GJB6基因外显子进行突变鉴定,对可疑的变异位点, Sanger测序检测家系其他成员该位点变异情况。结果 基因检测结果表明,家系先症者GJB6基因错义突变c.31G〉A,该突变导致连接蛋白-30（connexin-30, CX-30）第11位氨基酸由甘氨酸变成精氨酸（p.G11R）。家系的患者均携带此变异,而家系表型正常的个体不携带此变异。结论 GJB6基因c.31G〉A（p.G11R）突变是该有汗性外胚层发育不良家系致病基因突变。