【摘要】：遺傳性對稱性色素異常癥(Dyschromatosis symmetrica hereditaria, DSH, OMIM127400)亦稱為土肥肢端色素沉著癥(acropigmentation of Dohi),是一種較為少見的遺傳性皮膚病。該病的主要臨床表現(xiàn)為肢端對稱分布的色素沉著斑與色素減退斑,尤以手背和足背最為明顯,面部可有雀斑樣損害,日曬后皮損加重。嚴(yán)重者可累及四肢及全身,一般無自覺癥狀。通常在嬰兒期或者兒童期發(fā)病,青春期加重。電鏡上表現(xiàn)為黑素細(xì)胞數(shù)目的減少,在色素沉著區(qū)的黑素細(xì)胞出現(xiàn)代償性代謝水平的升高。本病通常表現(xiàn)為常染色體顯性遺傳,且有較高的外顯率。我國學(xué)者張學(xué)軍等已將本病的致病基因定位在1q11-1q21上,日本學(xué)者發(fā)現(xiàn)DSH致病基因?yàn)殡p鏈RNA特異性腺苷脫氨酶(DSRAD)基因。我們對4個(gè)DSH家系采用PCR和直接測序方法進(jìn)行突變檢測,以期發(fā)現(xiàn)DSRAD基因新突變,擴(kuò)大該基因的突變譜。 目的檢測遺傳性對稱性色素異常癥4個(gè)家系DSRAD基因的突變,擴(kuò)大該病的基因突變譜。 方法收集遺傳性對稱性色素異常癥4個(gè)家系的外周血標(biāo)本,采用PCR方法結(jié)合DNA直接測序的方法,檢測了4個(gè)家系成員中共13例患者及7例表型正常者和100例無親緣關(guān)系健康個(gè)體的DSRAD基因突變情況。 結(jié)果在家系A(chǔ)的所有患者中均檢測到DSRAD基因第11號外顯子的錯(cuò)義突變c.3,002GT(p. R1001L),第3002位堿基由G突變?yōu)門,導(dǎo)致第1001位密碼子精氨酸被亮氨酸取代。RT-PCR證實(shí)了這一突變。同時(shí)發(fā)現(xiàn)一個(gè)新的SNP：c.2496+30delT(IVS 7+30delT)。在家系B的患者中檢測到DSRAD基因第12號外顯子上一個(gè)新的移碼突變c.3089-3090delGA(p. R1030sX1036)。第3089-3090位的兩個(gè)堿基GA缺失導(dǎo)致移碼及過早的終止密碼子的產(chǎn)生。家系C中患者DSRAD基因12號外顯子第3159位堿基G缺失,即c.3159de1G,導(dǎo)致一新的移碼突變p.L1053fs→1076X；家系D中患者DSRAD基因13號外顯子第3209位和3210位堿基之間插入1個(gè)堿基C(c.3209insC),導(dǎo)致又一新的移碼突變p.L1070fs→1092X。 結(jié)論4個(gè)DSH家系患者均存在DSRAD基因新突變,可能由此引起編碼蛋白的結(jié)構(gòu)和功能的改變,致皮膚色素異常。
[Abstract]:Hereditary symmetrical pigmentation (Dyschromatosis symmetrica hereditaria, DSH, OMIM127400), also known as (acropigmentation of Dohi), is a rare hereditary skin disease. The main clinical manifestations of the disease were pigmentation spots and hypopigmentation spots distributed symmetrically on the extremities, especially on the back of the hand and the back of the foot. Severe can involve limbs and the whole body, generally without conscious symptoms. Usually in infancy or childhood, puberty is aggravated. Electron microscopy showed that the number of melanocytes decreased and the modern metabolic level of melanocytes in pigmented areas increased. The disease is usually autosomal dominant and has a high rate of exophthalmos. Zhang Xuejun, a Chinese scholar, has mapped the pathogenicity gene of the disease on 1q11-1q21. Japanese researchers have found that the DSH gene is a double-stranded RNA specific adenosine deaminase (DSRAD) gene. Four DSH families were detected by PCR and direct sequencing in order to find new mutations of DSRAD gene and expand the mutation profile of DSRAD gene. Objective to detect the mutation of DSRAD gene in 4 families with hereditary symmetrical dystrophy and to expand the gene mutation spectrum of the disease. Methods Peripheral blood samples were collected from 4 families with hereditary symmetrical dystrophy. PCR method combined with direct sequencing of DNA was used. DSRAD gene mutations in 13 patients, 7 normal phenotypes and 100 unrelated healthy individuals from 4 families were detected. Results the missense mutation c.3002GT (p.) of exon 11 of DSRAD gene was detected in all patients of family A. R1001L), where the 3002 base group mutated from G to T, leading to the substitution of arginine at codon 1001 by leucine. This mutation was confirmed by RT-PCR. A new SNP:c.2496 30delT (IVS 7 30delT) was also found. A new frameshift mutation c.3089-3090delGA on exon 12 of DSRAD gene was detected in patients with line B at home. R1030sX1036) The deletion of two bases GA at position 3089-3090 leads to the generation of frameshift and premature termination codon. In pedigree C, the deletion of the 3159 base G of exon 12 of the DSRAD gene, namely c. 3159de1G, led to a new frameshift mutation p.L1053fs 1076X. In family D, one base C (c.3209insC) was inserted between exon 3209 and 3210 of DSRAD gene, which led to a new frameshift mutation p.L1070fs 1092X. Conclusion there is a new mutation of DSRAD gene in 4 DSH families, which may lead to the change of the structure and function of the encoded protein and the abnormality of skin pigmentation.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R758.54

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1 張福仁;劉紅;蔣德科;田洪青;余龍;;遺傳性對稱性色素異常癥2例基因診斷[J];臨床皮膚科雜志;2008年05期

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