【摘 要】
:
Dystrophic epidermolysis bullosa is an inherited bullous dermatosis caused by COL7A1 gene mutation in autosomal dominant or recessive mode.COL7A1 gene encodes type Ⅶ collagen--the main component of th
【机 构】
:
四川省医学科学院·四川省人民医院人类疾病基因四川省重点实验室 四川省医学科学院·四川省人民医院皮肤
【出 处】
:
中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议
论文部分内容阅读
Dystrophic epidermolysis bullosa is an inherited bullous dermatosis caused by COL7A1 gene mutation in autosomal dominant or recessive mode.COL7A1 gene encodes type Ⅶ collagen--the main component of the anchoring fibrils at dermal-epidermal junction.Besides the 730 mutations reported in COL7A1 gene,we identified two novel mutations in a Chinese family,which caused recessive dystrophic epidermolysis bullosa(RDEB).The diagnosis was established histopathologically and ultrastructurally.After genomic DNA extraction from the peripheral blood sample of all subjects(5 pedigree members and 136 unrelated control individuals),COL7A1 gene screening was performed by polymerase chain reaction amplification and direct DNA sequencing of the whole coding exons and flanking intronic regions.Genetic analysis of COL7A1 gene in affected individuals revealed compound heterozygotes with identical novel mutations.The maternal mutation is 2-bp deletion at exon 8 of COL7A1 gene (c.1006_1007delCA),leading to a subsequent reading frame-shift and producing a premature termination codon located 48 amino acids downstream in exon 9(p.Q336EfsX48),consequently resulting in truncation of 2562 amino acids downstream.This was only present in two affected brothers,but not in all other unaffected family members.The paternal mutation is a 1-bp deletion occurring at the first base of intron 65(c.IVS5568+1 delG)that deductively changes the strongly conserved GT dinucleotide at the 5donor splice site of exon 65,results in subsequent reading-through into intron 65 and creates a stop codon immediately following the amino acids encoded by exon 65(GTAA→TAA).This is predicted to produce a truncated protein lacking of 1089 C-terminal amino acids downstream.This was found in all family members except one of two unaffected sisters.Both of the two mutations were observed concurrently only in two brother patients.Neither one was found in 136 unrelated Chinese control individuals.This study reveals novel disease-causing mutations in COL7A1 gene.
其他文献
The neuromuscular blocking agents(NMBAs) are widely used in anesthesia as muscle relaxant.The steroid skeleton,decorated with two ammonium groups at proper positions,provides an excellent core for exp
Cyclobutanones serve as important and versatile intermediates in organic synthesis.Previous studies have shown that 3-ethoxycyclobutanones can be utilized to construct useful synthetic compounds such
The class Ⅲ subfamily of receptor tyrosine kinases(RTKs),also called PDGFR family,includes KIT(SCFR),FMS(MCSFR or CSF-1R),FLT3,and PDGFR-α and-β.The class Ⅲ RTKs are key receptorsin the regulation of
Breast cancers are a heterogeneous group of diseases with distinct and complex mechanisms of pathogenesis.1 Triple-negative breast cancers(TNBC) form a subgroup of breast cancers with poor prognosis.T
Aurora kinases play crucial role in cell division by the orchestration of pivotal mitotic events.Over-expression of these serine/threonine kinases have been noted in a variety of solid tumors(viz.colo
目的 严重联合免疫缺陷病(severe combined immunodeficiency,SCID)为一组由不同基因异常所致严重T细胞缺乏或功能异常,并伴随B细胞功能异常的疾病.X-连锁严重联合免疫缺陷病(X-linked severe combined immunodeficiency,X-SCID)是最常见的SCID类型,本研究对一个确定患儿已故的疑为X-连锁严重联合免疫缺陷病1家系成员IL
目的 先天性白内障占儿童致盲性眼病的第二位,遗传性白内障约占1/3,其中常染色体显性遗传性白内障最为多见.本研究探索使用DNA测序技术对河南省一个5代常染色体显性遗传性核性白内障家系候选致病基因进行突变筛查和产前诊断的可行性.方法 签署知情同意书后,采集家系成员的外周静脉血,提取基因组DNA.选择国内外已报道的与先天性核性白内障发生相关的4个晶状体蛋白基因(CRYBA1/A3、CRYBB1、CRY
背景 血友病A(Hemophilia A,HA)是最常见的X连锁隐性遗传性出血性疾病,其最主要病因是由于凝血因子Ⅷ(FⅧ)基因缺陷而导致FⅧ含量不足或活性下降,从而引起凝血功能障碍,多表现为自发性出血不止或手术、创伤后出血不止.临床上根据患者凝血因子Ⅷ促凝活性(FⅧ:C)将其分为重型、中性和轻型,比例分别为50%,10%,40%,其中重型HA中有约50%的是由于F8基因内含子22倒位突变引起的[1
目的 探讨脊髓小脑共济失调3型患者的临床特点、分子遗传学特征及产前诊断的意义。方法 采用聚合酶链反应及DNA片段分析技术对脊髓小脑共济失调3型一家系4代共9例患者(其中1例为先证者之4月龄胎儿)中的2例患者施行SCA3/ATXN3基因(CAG)n重复数目分析。结果 一家系中4代共9例患者发病均符合常染色体显性遗传特征,其中8例患者(除外先证者之4月龄胎儿)均以步态不稳为首发症状,伴发不同程度构音障
目的 脊髓性肌萎缩症(Spinal Muscular Atrophy,SMA)发病原因主要是决定基因SMN1外显子7纯合缺失所导致,其修饰基因SMN2和NAIP的拷贝数影响患者临床表型,建立技术体系对SMN1,SMN2和NAIP基因拷贝数进行检测有助于对脊髓性肌萎缩症进行快速诊断。样本和方法 针对SMN1,SMN2,NAIP和参比基因的特异序列设计荧光TaqMan探针,优化反应条件,根据Ct值差异