可变性红斑角化症一家系GJB3和GJB4基因突变研究
发布时间：2018-09-17 17:04
【摘要】：研究背景可变性红斑角化症是一种少见的先天性遗传性皮肤病，主要是常染色体显性遗传。此病有两个显著的临床特点：迁移多变的红斑和相对固定的角化斑块。红斑可能是地图状、环状、匍形回状、靶形等，其形状、大小、位置在数小时到数天内均可不断变化。角化斑块位置和形状相对固定，多见于四肢伸侧、臀部及面部，大约50%可变性红斑角化症患者有弥漫性掌跖角化。可变性红斑角化症常在出生后第一年内发病,发病后病情持续进展，多数患者在青春期缓解，但难以痊愈。内外环境刺激如：压力、温度变化、摩擦、创伤、妊娠、日光曝晒、服用避孕药等均可使病情加重。可变性红斑角化症的致病基因为位于染色体1p34-35区域的GJB3和GJB4基因，，这两个基因分别编码缝隙连接蛋白connexin31(Cx31)和connexin30.3(Cx30.3)，控制细胞间联系，调节表皮分化功能，所以GJB3和GJB4基因突变均可导致可变性红斑角化症。迄今为止，国内外总共报道过13种GJB3基因突变和7种GJB4基因突变，其中GJB3基因有3种隐性突变，其余均为显性突变。 目的(1)检测一例中国汉族可变性红斑角化症家系的GJB3和GJB4基因的致病性突变。(2)探讨可变性红斑角化症基因型和临床表型之间的相关性。 方法抽取先证者及其父母、676例无亲缘关系的正常对照血样提取DNA，采用聚合酶链反应PCR扩增患者和健康对照GJB3和GJB4基因的全部外显子编码区及侧翼序列，应用ABI3730XL测序仪进行直接测序检测有无致病性突变。总结国内外文献，探讨可变性红斑角化症突变位点与临床表型之间的相关性。 结果测序结果显示先证者及其母亲在GJB3基因上的第134位碱基G突变为A，使不带电荷的甘氨酸变成带负电荷的谷基酸，即p.G45E，先证者的父亲及676例正常对照均未发现此突变点；所有个体中均未检测到GJB4基因突变。基因型与表型之间的相关性研究显示，可变性红斑角化症的突变位点与临床表型之间无明确关联。 结论(1)GJB3基因的一个错义突变（p.G45E）是该例可变性红斑角化症家系患者发病的主要分子遗传学基础，为进一步开展遗传咨询、产前基因诊断提供重要的前提。(2)可变性红斑角化症的突变位点与临床表型之间无明确关联。
[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.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.53
本文编号：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.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.53
【共引文献】
相关期刊论文 前2条
1 吴要群;张学军;杨森;;可变性红斑角皮病的分子遗传学进展[J];国际皮肤性病学杂志;2006年05期
2 周欣;田歆;杨艳;刘福荣;;可变性红斑角化症1例[J];中国皮肤性病学杂志;2011年08期
本文编号：2246560
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