可變性紅斑角化癥一家系GJB3和GJB4基因突變研究
發(fā)布時間：2018-09-17 17:04
【摘要】：研究背景可變性紅斑角化癥是一種少見的先天性遺傳性皮膚病，主要是常染色體顯性遺傳。此病有兩個顯著的臨床特點：遷移多變的紅斑和相對固定的角化斑塊。紅斑可能是地圖狀、環(huán)狀、匍形回狀、靶形等，其形狀、大小、位置在數(shù)小時到數(shù)天內(nèi)均可不斷變化。角化斑塊位置和形狀相對固定，多見于四肢伸側(cè)、臀部及面部，大約50%可變性紅斑角化癥患者有彌漫性掌跖角化�？勺冃约t斑角化癥常在出生后第一年內(nèi)發(fā)病,發(fā)病后病情持續(xù)進展，多數(shù)患者在青春期緩解，但難以痊愈。內(nèi)外環(huán)境刺激如：壓力、溫度變化、摩擦、創(chuàng)傷、妊娠、日光曝曬、服用避孕藥等均可使病情加重�？勺冃约t斑角化癥的致病基因為位于染色體1p34-35區(qū)域的GJB3和GJB4基因，，這兩個基因分別編碼縫隙連接蛋白connexin31(Cx31)和connexin30.3(Cx30.3)，控制細胞間聯(lián)系，調(diào)節(jié)表皮分化功能，所以GJB3和GJB4基因突變均可導致可變性紅斑角化癥。迄今為止，國內(nèi)外總共報道過13種GJB3基因突變和7種GJB4基因突變，其中GJB3基因有3種隱性突變，其余均為顯性突變。 目的(1)檢測一例中國漢族可變性紅斑角化癥家系的GJB3和GJB4基因的致病性突變。(2)探討可變性紅斑角化癥基因型和臨床表型之間的相關(guān)性。 方法抽取先證者及其父母、676例無親緣關(guān)系的正常對照血樣提取DNA，采用聚合酶鏈反應PCR擴增患者和健康對照GJB3和GJB4基因的全部外顯子編碼區(qū)及側(cè)翼序列，應用ABI3730XL測序儀進行直接測序檢測有無致病性突變�？偨Y(jié)國內(nèi)外文獻，探討可變性紅斑角化癥突變位點與臨床表型之間的相關(guān)性。 結(jié)果測序結(jié)果顯示先證者及其母親在GJB3基因上的第134位堿基G突變?yōu)锳，使不帶電荷的甘氨酸變成帶負電荷的谷基酸，即p.G45E，先證者的父親及676例正常對照均未發(fā)現(xiàn)此突變點；所有個體中均未檢測到GJB4基因突變�；蛐团c表型之間的相關(guān)性研究顯示，可變性紅斑角化癥的突變位點與臨床表型之間無明確關(guān)聯(lián)。 結(jié)論(1)GJB3基因的一個錯義突變（p.G45E）是該例可變性紅斑角化癥家系患者發(fā)病的主要分子遺傳學基礎(chǔ)，為進一步開展遺傳咨詢、產(chǎn)前基因診斷提供重要的前提。(2)可變性紅斑角化癥的突變位點與臨床表型之間無明確關(guān)聯(lián)。
[Abstract]:Background variable erythematosis is a rare congenital hereditary dermatosis, mainly autosomal dominant inheritance. The disease has two distinct clinical features: the variable migration of erythema and relatively fixed keratinized plaques. Erythema may be map shaped, ring shaped, creeping gyrus, target shape, etc. Its shape, size and position can change continuously within a few hours to several days. The position and shape of keratosis plaques are relatively fixed, most commonly seen in the extension of limbs, buttocks and faces, about 50% of patients with deformable erythematosis have diffuse palmar metatarsal keratosis. Erythematokeratosis of degeneration often occurs in the first year after birth and continues to progress after onset. Most patients are relieved during puberty but difficult to recover. External and internal environmental stimuli such as pressure, temperature changes, friction, trauma, pregnancy, sun exposure, contraceptive, etc. The pathogenetic genes of Erythrokeratosis are GJB3 and GJB4 genes located in the 1p34-35 region of chromosome. These two genes encode gap junction protein connexin31 (Cx31) and connexin30.3 (Cx30.3) respectively to control intercellular connections and regulate epidermal differentiation. Therefore, both GJB3 and GJB4 gene mutations can lead to degenerative erythematosis. Up to now, 13 GJB3 gene mutations and 7 GJB4 gene mutations have been reported at home and abroad. Three recessive mutations are found in GJB3 gene and the others are dominant mutations. Objective (1) to detect the pathogenicity mutations of GJB3 and GJB4 genes in a Chinese Han Chinese family with variable erythematosis. (2) to investigate the relationship between genotypes and clinical phenotypes of degenerative erythrokeratosis. Methods all exon coding regions and flanking sequences of GJB3 and GJB4 gene were amplified by polymerase chain reaction (PCR) PCR from 676 unrelated normal control blood samples from proband and their parents, and all exon coding regions and flanking sequences of GJB3 and GJB4 gene were amplified by polymerase chain reaction (PCR). ABI3730XL sequencing instrument was used to detect the pathogenicity of mutation by direct sequencing. To investigate the correlation between mutation loci and clinical phenotypes of erythematosis erythematosus at home and abroad. Results the sequencing results showed that the 134th base G of the proband and his mother in the GJB3 gene was mutated to A, and the uncharged glycine was transformed into the negatively charged glutamic acid, p. G45E.The father of the proband and 676 normal controls did not find this mutation. No mutation of GJB4 gene was detected in all individuals. The study on the relationship between genotype and phenotype showed that there was no clear correlation between the mutation site and the clinical phenotype of Erythrokeratosis. Conclusion (1) A missense mutation (p.G45E) of the GJB3 gene is the main molecular genetic basis of the disease in this family of patients with erythematosis erythematosus. Prenatal gene diagnosis provides an important prerequisite. (2) there is no clear correlation between mutation sites and clinical phenotypes in degenerative erythrokeratosis.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R758.53
本文編號：2246560
[Abstract]:Background variable erythematosis is a rare congenital hereditary dermatosis, mainly autosomal dominant inheritance. The disease has two distinct clinical features: the variable migration of erythema and relatively fixed keratinized plaques. Erythema may be map shaped, ring shaped, creeping gyrus, target shape, etc. Its shape, size and position can change continuously within a few hours to several days. The position and shape of keratosis plaques are relatively fixed, most commonly seen in the extension of limbs, buttocks and faces, about 50% of patients with deformable erythematosis have diffuse palmar metatarsal keratosis. Erythematokeratosis of degeneration often occurs in the first year after birth and continues to progress after onset. Most patients are relieved during puberty but difficult to recover. External and internal environmental stimuli such as pressure, temperature changes, friction, trauma, pregnancy, sun exposure, contraceptive, etc. The pathogenetic genes of Erythrokeratosis are GJB3 and GJB4 genes located in the 1p34-35 region of chromosome. These two genes encode gap junction protein connexin31 (Cx31) and connexin30.3 (Cx30.3) respectively to control intercellular connections and regulate epidermal differentiation. Therefore, both GJB3 and GJB4 gene mutations can lead to degenerative erythematosis. Up to now, 13 GJB3 gene mutations and 7 GJB4 gene mutations have been reported at home and abroad. Three recessive mutations are found in GJB3 gene and the others are dominant mutations. Objective (1) to detect the pathogenicity mutations of GJB3 and GJB4 genes in a Chinese Han Chinese family with variable erythematosis. (2) to investigate the relationship between genotypes and clinical phenotypes of degenerative erythrokeratosis. Methods all exon coding regions and flanking sequences of GJB3 and GJB4 gene were amplified by polymerase chain reaction (PCR) PCR from 676 unrelated normal control blood samples from proband and their parents, and all exon coding regions and flanking sequences of GJB3 and GJB4 gene were amplified by polymerase chain reaction (PCR). ABI3730XL sequencing instrument was used to detect the pathogenicity of mutation by direct sequencing. To investigate the correlation between mutation loci and clinical phenotypes of erythematosis erythematosus at home and abroad. Results the sequencing results showed that the 134th base G of the proband and his mother in the GJB3 gene was mutated to A, and the uncharged glycine was transformed into the negatively charged glutamic acid, p. G45E.The father of the proband and 676 normal controls did not find this mutation. No mutation of GJB4 gene was detected in all individuals. The study on the relationship between genotype and phenotype showed that there was no clear correlation between the mutation site and the clinical phenotype of Erythrokeratosis. Conclusion (1) A missense mutation (p.G45E) of the GJB3 gene is the main molecular genetic basis of the disease in this family of patients with erythematosis erythematosus. Prenatal gene diagnosis provides an important prerequisite. (2) there is no clear correlation between mutation sites and clinical phenotypes in degenerative erythrokeratosis.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R758.53
【共引文獻】
相關(guān)期刊論文 前2條
1 吳要群;張學軍;楊森;;可變性紅斑角皮病的分子遺傳學進展[J];國際皮膚性病學雜志;2006年05期
2 周欣;田歆;楊艷;劉福榮;;可變性紅斑角化癥1例[J];中國皮膚性病學雜志;2011年08期
本文編號：2246560
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