KRT9基因突变所致表皮松解性掌跖角化病1例

报告KRT9基因突变所致表皮松解性掌跖角化病1例.患者男,中国籍,32岁,手足角化性斑块30余年.皮肤科检查:双侧掌跖面可见对称性弥漫性角化斑块,皮肤粗糙增厚,呈灰黄色.皮损组织病理:表皮明显角化过度,颗粒层棘层增厚,皮突延长,颗粒细胞变性,考虑掌跖角化病.基因全外显子组测序结果:KRT9基因外显子检测出c.487C＞...     

表皮松解掌跖角化症KRT9基因突变的研究进展

表皮松解性掌跖角化症(EPPK)是一种通常由位于17q12染色体上KRT9突变导致的常染色体显性遗传性皮肤病。本文综述了目前为止,EPPK家系中KRT9突变的类型及特点。通常认为KRT9基因突变热区位于螺旋结构的杆状功能域1A区和2B区。随着EPPK家系病例的不断积累,在K9的头部也已检出突变位点,不再局限于螺旋结构杆状结构域。     

表皮松解性掌跖角皮症一家系KRT9基因新突变

目的:检测表皮松解性掌跖角皮症一家系患者角蛋白9(KRT9)基因突变。方法:收集家系成员的临床资料和血样,提取家系中4例患者和3名正常人及50名与本家系无关的正常对照外周血DNA,采用PCR技术扩增KRT9基因所有编码区并进行测序,分别检测家系中的突变情况。结果:该家系中所有患者均存在KRT9基因错义突变(c.484TC),导致第162位密码子由TCT(丝氨酸)转变为CCT(脯氨酸)(p.S162P),家系中3名正常个体和50名健康对照均未发现上述突变。结论:KRT9基因c.484TC错义突变是导致该家系发生表皮松解性掌跖角皮症的遗传基础。     

表皮松解性掌跖角化病1例

报告1例表皮松解性掌跖角化病。患者女,26岁。双侧掌跖角化20余年。皮肤科检查见双侧掌跖对称性角化性斑块。皮损组织病理检查示表皮角化过度,颗粒层增厚,棘层及颗粒层中有较多裂隙,裂隙处细胞界限不清,由淡染物质或透明角质颗粒组成。组织病理改变符合表皮松解性掌跖角化病诊断。采用阿维A治疗后皮损明显改善。     

一个表皮松解性掌跖角化病家系的KRT1基因突变分析

目的 探讨一个中国汉族人表皮松解性掌跖角化病(EPPK)家系的角蛋白基因KRT1、KRT9、KRT10突变情况.方法 收集1个EPPK家系的临床资料,提取外周血DNA,通过PCR扩增角蛋白KRT1、KRT9、KRT10基因编码区的全部外显子及其侧翼序列并测序,以表型正常家系成员及50例健康人为正常对照.结果 发现家系内6例患者均存在KRT1基因错义突变c.1436T>C,导致第479位的异亮氨酸被苏氨酸取代(I479T),在家系中6例正常人及50例对照者未发现上述突变.结论 错义突变KRTI的c.1436T>C可能为导致该家系临床表型的主要原因.本例为国内首次发现的KRT1突变引起的EPPK家系.

Abstract：

Objective To analyze the mutations in keratin 1 (KRT1), KRT9 and KRT10 genes in a Chinese family with epidermolytic palmoplantar keratoderma (EPPK). Methods Clinical data were collected from a family with EPPK. Genomic DNA was extracted from the peripheral blood of 12 family members, including 6 patients and 6 unaffected members, as well as from 50 unrelated normal human controls. PCR was performed to amplify all the exons and flanking sequences of KRT1, KRT9 and KRT10 genes followed by DNA sequencing.Results A missense mutation C.1436T > C was found in the highly conserved helix termination motif of KRT1 gene of all the patients, resulting in a substitution of isoleucine by threonine at position 479 of the KRT1 protein. No mutation was found in the unaffected members or unrelated controls. Conclusions The missense mutation C.1436T > C in K.RT1 gene is likely to be the main cause of the phenotype of EPPK in this family.This is the first report of a pedigree with KRT1 gene mutation-induced EPPK in China.     

三个表皮松解性掌跖角化症家系KRT9基因突变的研究

目的 探讨表皮松解性掌跖角化症家系的KRT9基因突变与临床表现的关系。方法 PCR扩增KRT9基因编码氨基酸的7个外显子,对扩增产物进行变性高效液相色谱分析、DNA测序。结果 在所研究的3个EPPK家系中,发现KRT9基因第1外显子第497位核苷酸A缺失并插入GGCT,导致角蛋白9分子第166位酪氨酸缺失并插入色氨酸和亮氨酸,即Y166delinsWL。片段特异性PCR证实了该突变不是一个常见的多态性,而是国际中间纤维突变库(http://www.interfil.org)中未报道过的一种新突变。结论 KRT9基因497delAinsGGCT突变可能是部分中国人EPPK患者发病的遗传基础。     

表皮松解性掌跖角化症遗传学研究进展

表皮松解性掌跖角化症是一种以掌跖表皮过度角化为主要特征的先天性遗传病.本文阐述了角蛋白分子的结构、分类以及由角蛋白突变所引起的一些遗传性角蛋白病,总结了迄今所发现的导致表皮松解性掌跖角化症的21种不同的角蛋白9基因突变类型及蛋白改变,在各个种族或民族中开展的有关角蛋白基因突变的研究情况.     

表皮松解性掌跖角化病二家系基因突变检测

目的：检测表皮松解性掌跖角化病二家系患者致病基因。方法：收集二家系资料,提取二家系成员及100名（无亲缘关系）正常对照血样DNA,采取聚合酶链反应技术对KRT1、KRT9和KRT16基因进行扩增,并对其产物进行测序。结果：家系1先证者中检测到 KRT1基因突变c.598T>C（p.F200L）。家系2三例患者中检测到KRT9基因含杂合突变c.488G>A（p.R163Q）。而家系正常成员及家系外无亲缘关系的100名正常对照中均不存在以上突变。结论：本研究表皮松解性掌跖角化病二家系发病与KRT1、KRT9基因突变有关,且KRT1基因突变p.F200L为国内首次报道。     

弥漫性表皮松解性掌跖角化病1例

1病历摘要 先证者，女，3岁。因掌跖部皮肤弥漫性增厚，于2007年6月来我院皮肤科就诊。患儿出生后2个月，掌跖部皮肤开始出角化过度，随年龄增加病情逐渐加重。曾在多家医院予以维甲酸类药物治疗，症状可缓解但停药即复发。[第一段]     

弥漫性非表皮松解性掌跖角化病1例

1病历摘要 患者女,42岁。闲双侧掌跖角化40余年,于2006年9月来我院就诊。患者自婴儿期起无明显诱凶双手掌出现对称性片状红斑,角化,形状不规则．受累皮肤粗糙增厚,同时累及双足和甲板,指（趾）甲增厚、浑浊,呈灰黄色。皮损逐渐向周同扩展,至青春期时已经累及双手整个掌侧、腕部及于背的大部分,双足跖和足背亦呈弥漫性角化过度,跖部较重,皮损呈对称性,     

A novel mutation of keratin 9 in a large Chinese family with epidermolytic palmoplantar keratoderma

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by diffuse yellow thickening of the skin of the palms and soles, sharply bordered with erythematous margins. Histologically and ultrastructurally, EPPK presents cytolysis of keratinocytes and abnormal aggregation of tonofilaments in the suprabasal layers of the epidermis. To date, 15 different mutations of the keratin 9 gene (KRT9) have been demonstrated to cause most cases of EPPK. OBJECTIVES: To identify the KRT9 mutation in a large Chinese family with EPPK. METHODS: Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific polymerase chain reaction (AS-PCR) were used to screen exon 1 of the KRT9 gene for sequence variations. RESULTS: The DHPLC elution profiles of the DNA fragments amplified from the affected samples differed from those obtained from unaffected individuals, indicating that a sequence variation existed within the analysed fragment of KRT9. DNA sequencing revealed a novel insertion-deletion mutation in the exon 1 of KRT9, 497delAinsGGCT, resulting in the change of tyrosine(166) to tryptophan and leucine (Y166delinsWL). AS-PCR confirmed the mutation was not a common polymorphism. CONCLUSIONS: The results suggest the molecular basis of EPPK in this Chinese family and provide further evidence that mutations in the helix initiation motif of keratin 9 underlie Chinese EPPK.     

A keratin 9 Gene mutation (Asn160Ser) in a Japanese patient with epidermolytic palmoplantar keratoderma

We described a 5-year-old Japanese girl with epidermolytic palmoplantar keratoderma and examined her for a keratin 9 gene mutation. Physical examination disclosed diffuse yellowish hyperkeratosis with an erythematous border limited strictly to the palms and soles. Histological examination revealed hyperkeratosis with vacuolar degeneration in the spinous and granular layers of the epidermis. Sequence analysis demonstrated an A to G transition at the middle position of codon 160 in the 1A domain of the keratin 9 gene. The amino acid at codon 160 was deduced to have changed from asparagine (Asn) to serine (Ser). This is the first case with an Asn160Ser mutation in a Japanese. The substitution of Ser for Asn at codon 160 of the keratin 9 gene is assumed to be fatal for keratin filament assembly regardless of race or ethnicity.     

Keratin 9 gene mutations in five Korean families with epidermolytic palmoplantar keratoderma

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease characterized clinically by localized palmoplantar thickening and histopathologically by granular degeneration of the epidermis. Recent molecular biological studies have revealed that EPPK is caused by mutations of the keratin 9 gene in sequences mainly encoding the highly conserved 1 A rod domain. Here we demonstrate a novel mutation of N160H (position 8 of the 1 A domain) and two other previously reported mutations, R162W and N160S, in five unrelated Korean families with EPPK. The three-dimensional structure of the 1 A domain of the related vimentin intermediate filament protein chain is now known. Based on its likely similarity to the keratin 9 chain, we predict that inappropriate amino acid substitutions in position 10 of 1 A will likely interfere with coiled-coil dimer stability, and those in position 8 will interfere with tetramer stability. Accordingly, these mutations compromise the structural integrity of the keratin intermediate filaments leading to the pathology of EPPK.     

Keratin-9 gene mutation in a family with epidermolytic palmoplantar keratoderma

BACKGROUND: Epidermolytic palmoplantar keratoderma is an autosomal dominant inherited disorder of keratinization. METHODS: We studied five members of a Jewish family with epidermolytic palmoplantar keratoderma. Genomic DNA was extracted from leucocytes, and exon 1 of the keratin 9 gene was amplified using polymerase chain reaction techniques. RESULTS: The mutation was found in exon 1 of the keratin 9 gene in codon 160. CONCLUSIONS: Like most of the other families with clinical features of epidermolytic palmoplantar keratoderma the mutation is found in exon 1 of the keratin 9 gene.