1個(gè)表皮松解性掌跖角化癥和2個(gè)Ⅰ型先天性甲肥厚家系的基因型—表型相關(guān)性研究
發(fā)布時(shí)間：2018-12-06 08:01
【摘要】：背景：表皮松解性掌跖角化癥(EPPK)是一種較為常見的常染色體顯性遺傳病,主要由KRT9基因突變造成；先天性甲肥厚(PC)為一種相對罕見的常染色體顯性遺傳皮膚病,一般由KRTl6、KRT6A、KRT17和KRT6B基因突變所致。 目的：明確EPPK和PC-1的表型-基因型相關(guān)性。 方法：收集了1個(gè)EPPK家系和2個(gè)PC-1家系。EPPK家系的成年男性患者伴發(fā)先天性指屈曲(國際首報(bào))。通過單體型連鎖分析、PCR-DNA測序及RFLP確定和驗(yàn)證EPPK的基因突變；用長片段PCR+巢式PCR+DNA測序+RT-PCR方法,對KRT16、KRT6A、KRT17和KRT6B進(jìn)行突變檢測和驗(yàn)證。 結(jié)果：KRT9上、下游的微衛(wèi)星標(biāo)志D17S1787和D17S579與EPPK共分離,患者均攜帶KRT9第6外顯子c.T1373C(p.L458P)突變。在2個(gè)PC-1家系中,患者分別攜帶1個(gè)de novo型KRT6A剪接接受位點(diǎn)突變：IVS8-2AC(p.S487FfsX72)以及1個(gè)de novo型KRTl6第1外顯子雜合置換突變：c. AA373_374GG(p.N125G).3種基因突變在文獻(xiàn)中均未見報(bào)道(2011年《European Journal of Dermotology》第21卷第5期和修回中)。 結(jié)論：KRT9基因p.L458P突變較已報(bào)道的p.L458F引起的EPPK表型更為嚴(yán)重,故KRT9可能在EPPK伴指節(jié)墊和指屈曲中具有復(fù)雜的致病效應(yīng)。KRTl6基因p.N125G突變與已報(bào)道的p.N125D和p.N125S所致的表型均不相同,PC-1與KRT16第125位密碼子的不同突變類型有一定的對應(yīng)關(guān)系；KRT6A基因IVS8-2AC突變則表現(xiàn)為典型的PC癥狀,但伴有尚未報(bào)道的陰囊舌表型。EPPK和PC-1的基因型-表型相關(guān)性尚有待進(jìn)一步研究和證實(shí)。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R758.71
本文編號：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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R758.71
【共引文獻(xiàn)】
相關(guān)期刊論文 前3條
1 殷鑫湞;張寶榮;丁美萍;張灝;夏昆;胡正茂;;兩個(gè)彌漫性掌跖角化病家系的病理特征與基因突變分析[J];遺傳;2007年03期
2 張寶榮,殷鑫湞,夏昆,丁美萍,胡正茂,鄭敏,劉志蓉,夏家輝;一個(gè)表皮松解性掌跖角化病家系的KRT9基因突變分析[J];中華醫(yī)學(xué)遺傳學(xué)雜志;2004年06期
3 李明;華�？�;楊莉佳;朱小紅;戴迅毅;蔣屏東;;彌漫性掌跖角化病伴關(guān)節(jié)墊一家系20例[J];中華醫(yī)學(xué)遺傳學(xué)雜志;2006年05期
相關(guān)博士學(xué)位論文 前1條
1 郭碧蓉;全基因組外顯子測序發(fā)現(xiàn)點(diǎn)狀掌跖角化病致病基因COL14A1[D];安徽醫(yī)科大學(xué);2012年
相關(guān)碩士學(xué)位論文 前3條
1 何新輝;4個(gè)中國人表皮松解性掌跖角化癥家系KRT9基因突變的研究[D];中國科學(xué)院研究生院（上海生命科學(xué)研究院）;2004年
2 殷鑫湞;兩個(gè)亨廷頓舞蹈病大家系的臨床、影像學(xué)特征及基因突變分析[D];浙江大學(xué);2005年
3 唐斌;表皮松解掌跖角化癥一家系KRT9基因突變的分子遺傳學(xué)研究[D];暨南大學(xué);2010年
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