本文關鍵詞： 遺傳性對稱性色素異常癥 ADAR基因 突變　出處：《中國醫(yī)科大學》2010年碩士論文　論文類型：學位論文

【摘要】： 研究背景 遺傳性對稱性色素異常癥(Dyschromatosis Symmetrica Hereditaria,, DSH; OMIM 127400)又稱Dohi對稱性肢端色素沉著,是一種少見的常染色體顯性遺傳性皮膚病。該病最先由日本學者Toyama于1910年描述,并于1929年正式提出命名。DSH的典型表現(xiàn)為肢端對稱分布的色素沉著斑和色素減退斑,尤以手背和足背部位最為明顯,亦可延及前臂及小腿,呈網(wǎng)狀。部分患者面部可見雀斑樣色素沉著,一般無自覺癥狀。2003年日本學者Miyamura等發(fā)現(xiàn)ADAR基因是本病的致病基因,位于1q21.3約500kb關鍵區(qū)域。遺傳性泛發(fā)性色素異常癥(Dyschromatosis Universalis Hereditaria,, DUH; OMIM 127500)是一種少見的常染色體顯性遺傳性皮膚病,皮損主要表現(xiàn)為全身泛發(fā)性色素沉著斑和色素減退斑。早期研究認為,遺傳性對稱性色素異常癥是該病的一種亞型,近年隨著對致病基因的深入研究,發(fā)現(xiàn)遺傳性對稱性色素異常癥和遺傳性泛發(fā)性色素異常癥是兩類不同的疾病。屈側網(wǎng)狀色素沉著癥(Reticular pigmented anomaly of the flexures, RPAF; OMIM 179850)又稱Dowling-Degos病(Dowling-Degos disease, DDD),是一種少見的常染色體顯性遺傳性皮膚病。其臨床特征是對稱性的褐色斑疹,漸擴展融合成網(wǎng)狀,好發(fā)在腹股溝、股內側、腋下、腕、頸等屈側部位,多于青春期發(fā)病。DSH、DUH與DDD在臨床表現(xiàn)及病理改變上有許多相似之處,基因學診斷是鑒別的主要方法。 目的 1、尋找家系ADAR基因突變位點； 2、對疑似患者進行基因學診斷。 方法 1、整理家系資料,分析臨床表型； 2、針對DSH、DUH、DDD選擇STR markers,對家系進行連鎖分析； 3、采用PCR反應擴增ADAR基因的15個外顯子編碼區(qū)及側翼序列,用直接測序的方法對所有病例進行ADAR基因的突變檢測。 結果 1、家系四代隨代數(shù)增加,由典型表現(xiàn)(手背、足背、肘、膝等部位網(wǎng)狀色素沉著與減退的網(wǎng)狀斑)演變?yōu)閮H在面部出現(xiàn)的雀斑樣痣,臨床表現(xiàn)有明顯漸輕趨勢；部分患者出現(xiàn)唇周改變,在以往文獻中未曾報道。 2、測序回報在ADAR基因的15個外顯子編碼區(qū)及側翼序列中未發(fā)現(xiàn)突變基因。 3、在染色體1q22的微衛(wèi)星標記(chr1：154528835-154528881)處確定連鎖,排除了致病基因與染色體6q24.2-q25.2,12q21-q22,12q13的定位區(qū)域連鎖。 4、疑似患者在確定連鎖的位點無共享條帶,從而除外DSH。 結論 1、發(fā)現(xiàn)該家系病例隨代數(shù)增加,其臨床癥狀有減輕趨勢；部分患者有未曾報道的臨床表現(xiàn)； 2、在距DSH致病基因ADAR 5000kb處確定連鎖；排除了DUH、DDD的可能; 3、排除疑似患者患病的可能； 4、該家系病例ADAR基因的15個外顯子編碼區(qū)及側翼序列未見異常,提示致病基因可能位于內含子區(qū)域、5’端的啟動子區(qū)域或者ADAR附近的其它基因,有待下一步繼續(xù)研究。
[Abstract]:Research background. Dyschromatosis Symmetrica (DSH; OMIM 127400), also known as Dohi symmetric acropigmentation, is a rare autosomal dominant hereditary dermatosis. The disease was first described by Japanese scholar Toyama in 1910. In 1929, it was formally proposed that the typical expression of .DSH is pigmentation spots and hypopigmentation spots distributed symmetrically at the extremities, especially in the back of the hand and the dorsal part of the foot, and also in the forearm and the lower leg. In 2003, Japanese scholar Miyamura and others found that ADAR gene was the pathogenic gene of the disease. Dyschromatosis Universalis Hereditariaanus (DUH; OMIM 127500) is a rare autosomal dominant hereditary dermatosis, which is mainly characterized by systemic generalized pigmentation and hypopigmentation. Hereditary symmetrical dystrophy is a subtype of the disease. In recent years, with the in-depth study of pathogenic genes, It has been found that hereditary symmetrical dystrophy and hereditary generalized dyskinesia are two different diseases. Flexular pigmented anomaly of the flexures (RPAF; OMIM 179850), also known as Dowling-Degos disease Dowling-Degos disease, is a rare autosomal disease. Sexual hereditary dermatosis. Its clinical features are symmetrical brown macules, It is more common in inguinal, medial femoral, armpit, wrist, neck and equal flexion than puberty. DUH and DDD have many similarities in clinical manifestations and pathological changes. Genetic diagnosis is the main method to differentiate. Purpose. 1. To find the mutation site of ADAR gene in families; 2. Genetic diagnosis of suspected patients. Method. 1. Sorting out the family data and analyzing the clinical phenotype; (2) STR markers were selected for DUHD-DDD, and linkage analysis was carried out on the families. 3. The 15 exon coding regions and flanking sequences of ADAR gene were amplified by PCR reaction, and the mutation of ADAR gene was detected by direct sequencing in all cases. Results. 1. The four generations of pedigree increased with algebra, from typical manifestations (reticular pigmentation and decreased reticular plaques on the back of hand, back of foot, elbow, knee, etc.) to freckle nevus, which appeared only on the face. Some patients had perilabial changes, which had not been reported in previous literature. 2. No mutant gene was found in 15 exon coding regions and flanking sequences of ADAR gene by sequencing. 3. The linkage was confirmed at the microsatellite marker chr1: 154528835-154528881 of chromosome 1q22, which excluded the linkage between the pathogenic gene and the locational region of chromosome 6q24.2-q25.2C12q21-q2212q13. 4. The suspected patients had no shared bands at the identified linkage sites, with the exception of DSHs. Conclusion. 1. It was found that the clinical symptoms of the family increased with the increase of algebra, and some of the patients had unreported clinical symptoms. (2) the linkage was confirmed at 5000kb from the DSH pathogenic gene ADAR, and the possibility of DUHD-DDD was excluded. (3) to rule out the possibility of suspected patient becoming ill; 4. The 15 exon coding regions and flanking sequences of ADAR gene were not abnormal, suggesting that the pathogenic gene might be located in the promoter region of intron region 5'or other genes near ADAR.
【學位授予單位】：中國醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2010
【分類號】：R758.5

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