1个表皮松解性掌跖角化症和2个Ⅰ型先天性甲肥厚家系的基因型—表型相关性研究
发布时间：2018-12-06 08:01
【摘要】：背景：表皮松解性掌跖角化症(EPPK)是一种较为常见的常染色体显性遗传病,主要由KRT9基因突变造成；先天性甲肥厚(PC)为一种相对罕见的常染色体显性遗传皮肤病,一般由KRTl6、KRT6A、KRT17和KRT6B基因突变所致。 目的：明确EPPK和PC-1的表型-基因型相关性。 方法：收集了1个EPPK家系和2个PC-1家系。EPPK家系的成年男性患者伴发先天性指屈曲(国际首报)。通过单体型连锁分析、PCR-DNA测序及RFLP确定和验证EPPK的基因突变；用长片段PCR+巢式PCR+DNA测序+RT-PCR方法,对KRT16、KRT6A、KRT17和KRT6B进行突变检测和验证。 结果：KRT9上、下游的微卫星标志D17S1787和D17S579与EPPK共分离,患者均携带KRT9第6外显子c.T1373C(p.L458P)突变。在2个PC-1家系中,患者分别携带1个de novo型KRT6A剪接接受位点突变：IVS8-2AC(p.S487FfsX72)以及1个de novo型KRTl6第1外显子杂合置换突变：c. AA373_374GG(p.N125G).3种基因突变在文献中均未见报道(2011年《European Journal of Dermotology》第21卷第5期和修回中)。 结论：KRT9基因p.L458P突变较已报道的p.L458F引起的EPPK表型更为严重,故KRT9可能在EPPK伴指节垫和指屈曲中具有复杂的致病效应。KRTl6基因p.N125G突变与已报道的p.N125D和p.N125S所致的表型均不相同,PC-1与KRT16第125位密码子的不同突变类型有一定的对应关系；KRT6A基因IVS8-2AC突变则表现为典型的PC症状,但伴有尚未报道的阴囊舌表型。EPPK和PC-1的基因型-表型相关性尚有待进一步研究和证实。
[Abstract]:Background: epidermolytic palmoplantar keratosis (EPPK) is a common autosomal dominant hereditary disease mainly caused by KRT9 gene mutation. Congenital nail hypertrophy (PC) is a relatively rare autosomal dominant skin disease caused by mutations in KRTl6,KRT6A,KRT17 and KRT6B genes. Objective: to determine the phenotypic correlation between EPPK and PC-1. Methods: one EPPK family and two PC-1 families were collected. Adult male patients from EPPK family had congenital finger flexion. By haplotype linkage analysis, PCR-DNA sequencing and RFLP, EPPK gene mutations were identified and verified, and KRT16,KRT6A,KRT17 and KRT6B mutations were detected and verified by long PCR nested PCR DNA sequencing RT-PCR method. Results: on KRT9, the downstream microsatellite markers D17S1787 and D17S579 were coisolated with EPPK. All patients carried c.T1373C (p.L458P) mutation in exon 6 of KRT9. In two PC-1 families, the patients carried one de novo type KRT6A splicing acceptance site mutation: IVS8-2AC (p.S487FfsX72) and one de novo KRTl6 exon 1 heterozygosity mutation: C. AA373_374GG (p.N125G). None of the three gene mutations were reported in the literature (2011 < European Journal of Dermotology > vol. 21, No. 5 and revision). Conclusion: the p.L458P mutation of KRT9 gene is more serious than the reported EPPK phenotype induced by p.L458F. Therefore, KRT9 may have complex pathogenicity in EPPK with knuckle pad and finger flexion. The p.N125G mutation of KRTl6 gene is different from the phenotypes caused by reported p.N125D and p.N125S. There was a certain correspondence between PC-1 and the different mutation types of codon 125 of KRT16. The IVS8-2AC mutation of KRT6A gene showed typical PC symptoms, but with unreported scrotal tongue phenotype. The genotypic correlation between EPPK and PC-1 remains to be further studied and confirmed.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.71
本文编号：2365711
[Abstract]:Background: epidermolytic palmoplantar keratosis (EPPK) is a common autosomal dominant hereditary disease mainly caused by KRT9 gene mutation. Congenital nail hypertrophy (PC) is a relatively rare autosomal dominant skin disease caused by mutations in KRTl6,KRT6A,KRT17 and KRT6B genes. Objective: to determine the phenotypic correlation between EPPK and PC-1. Methods: one EPPK family and two PC-1 families were collected. Adult male patients from EPPK family had congenital finger flexion. By haplotype linkage analysis, PCR-DNA sequencing and RFLP, EPPK gene mutations were identified and verified, and KRT16,KRT6A,KRT17 and KRT6B mutations were detected and verified by long PCR nested PCR DNA sequencing RT-PCR method. Results: on KRT9, the downstream microsatellite markers D17S1787 and D17S579 were coisolated with EPPK. All patients carried c.T1373C (p.L458P) mutation in exon 6 of KRT9. In two PC-1 families, the patients carried one de novo type KRT6A splicing acceptance site mutation: IVS8-2AC (p.S487FfsX72) and one de novo KRTl6 exon 1 heterozygosity mutation: C. AA373_374GG (p.N125G). None of the three gene mutations were reported in the literature (2011 < European Journal of Dermotology > vol. 21, No. 5 and revision). Conclusion: the p.L458P mutation of KRT9 gene is more serious than the reported EPPK phenotype induced by p.L458F. Therefore, KRT9 may have complex pathogenicity in EPPK with knuckle pad and finger flexion. The p.N125G mutation of KRTl6 gene is different from the phenotypes caused by reported p.N125D and p.N125S. There was a certain correspondence between PC-1 and the different mutation types of codon 125 of KRT16. The IVS8-2AC mutation of KRT6A gene showed typical PC symptoms, but with unreported scrotal tongue phenotype. The genotypic correlation between EPPK and PC-1 remains to be further studied and confirmed.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.71
【共引文献】
相关期刊论文 前3条
1 殷鑫浈;张宝荣;丁美萍;张灏;夏昆;胡正茂;;两个弥漫性掌跖角化病家系的病理特征与基因突变分析[J];遗传;2007年03期
2 张宝荣,殷鑫浈,夏昆,丁美萍,胡正茂,郑敏,刘志蓉,夏家辉;一个表皮松解性掌跖角化病家系的KRT9基因突变分析[J];中华医学遗传学杂志;2004年06期
3 李明;华海康;杨莉佳;朱小红;戴迅毅;蒋屏东;;弥漫性掌跖角化病伴关节垫一家系20例[J];中华医学遗传学杂志;2006年05期
相关博士学位论文 前1条
1 郭碧蓉;全基因组外显子测序发现点状掌跖角化病致病基因COL14A1[D];安徽医科大学;2012年
相关硕士学位论文 前3条
1 何新辉;4个中国人表皮松解性掌跖角化症家系KRT9基因突变的研究[D];中国科学院研究生院（上海生命科学研究院）;2004年
2 殷鑫浈;两个亨廷顿舞蹈病大家系的临床、影像学特征及基因突变分析[D];浙江大学;2005年
3 唐斌;表皮松解掌跖角化症一家系KRT9基因突变的分子遗传学研究[D];暨南大学;2010年
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