HOXD13基因多聚丙氨酸延展突变致一独特临床表现的并指（趾）多指（趾）家系

发布时间：2018-01-13 21:37

本文关键词：HOXD13基因多聚丙氨酸延展突变致一独特临床表现的并指（趾）多指（趾）家系　出处：《吉林大学》2011年硕士论文　论文类型：学位论文

更多相关文章： SPD HOXD13 PAE 突变分析

【摘要】：并指(趾)多指(趾)畸形(SPD)是HOXD13基因多聚丙氨酸延展突变引起的以常染色体显性遗传为特点的先天性肢体畸形。SPD典型的临床表现为,手部第3/4指并指,足部第4/5趾并趾。表型较重者可出现手部第4指复指和足部第4趾复指,症状极严重的SPD病例还会出现尿道下裂。三种遗传上不同的SPD位点已经被确定,分别为SPD1、SPD3和SPD3。 HOX基因编码一个转录因子超家族,很多研究证实,HOX基因在胚胎发育过程中起着重要的作用。HOX基因共有HOXA、HOXB、HOXC、HOXD四个基因簇,分别位于不同的染色体上。HOXD13位于HOXD簇最5′端,有两个外显子,其中外显子1包含一个不完全的三核苷酸重复序列,编码一个由15个丙氨酸残基组成的多聚丙氨酸片段。多聚丙氨酸链延展突变可导致SPD1,很多研究都认为少于6个丙氨酸插入不能引起临床表现,是没有致病性的。我们调查了一个三代的中国家系,其中受影响的3个个体表现为三种变易的手足畸形。我们对该家系进行详细的资料收集整理。对3名患者进行详细的临床查体,并对患者的双手双脚拍摄数码照片和X线片。在获得知情同意后,抽取患者及直系亲属外周血样,对先证者进行核型分析,并从患者、患者直系亲属及100名对照志愿者外周抗凝血中提取DNA。-20度储存备用,设计引物对HOXD13两外显子进行PCR,产物送生物公司测序。最终核型分析结果显示,未发现染色体结构和数目的异常。家系中所有三名受影响个人的HOXD13基因第1外显子多聚丙氨酸链区域插入了27bp的三核苷酸重复突变(c. 186- 212dup)。此种突变未出现在家系中所有未受影响个人及无关对照个体。在对照组中我们也没有发现重复序列的多态性证据。此家系的特点为:第2到5指的屈指畸形和关节融合、横向指骨、第三掌骨和近节指骨的骨融合,轻微的临床表型和更为严重的临床表型共存。这项研究扩展了HOXD13基因PAE突变的表型谱,为多聚丙氨酸重复序列多态性本质提供了更多的信息。另外,此家系独特的临床表型也使我们对SPD有了进一步的认识。
[Abstract]:Finger (toe) and multi finger (toe) malformation (SPD) is HOXD13 gene polyalanine expansion mutation caused by autosomal dominant congenital limb malformation clinical characteristics of typical.SPD, hand 3/4 and 4/5, the foot toe and toe phenotype may appear serious. Hand fourth fingers and fourth toes foot anaphoric anaphora, symptoms of serious SPD cases of hypospadias. There will be three kinds of different SPD genetic loci have been identified, respectively SPD1, SPD3 and SPD3.
The HOX gene encoding a transcription factor superfamily, many studies have confirmed that HOX gene in embryonic development process plays an important role in.HOX gene were HOXA, HOXB, HOXC, HOXD four gene clusters were located on different chromosomes in.HOXD13 HOXD cluster the 5 'end of two exons. Exon 1 contains an incomplete trinucleotide repeat sequence encoding a 15 alanine residue polyalanine fragment. Polyalanine expansion mutation can lead to SPD1, many studies have suggested that less than 6 of alanine causes clinical manifestations can not be inserted, is not pathogenic.
We investigated a three generation Chinese family, which affected 3 individuals for three limbs deformity. Variation of us for detailed information collected on the family. In 3 patients with the clinical examination, and take digital photographs and X ray on patients with hands and feet. After informed consent was obtained from patients and relatives, peripheral blood samples, karyotype analysis of the proband, and from patients, patients with relatives and 100 control volunteers in peripheral blood from DNA.-20 storage backup, design primers on two HOXD13 exons of PCR, were sequenced.
The karyotype analysis showed that no abnormal chromosome number and structure. The family of all three affected individuals of the HOXD13 gene exon first polyalanine region inserted 27bp trinucleotide repeat mutations (C. 186- 212dup). The mutation does not appear in the family all the unaffected individuals and independent the control subjects in the control group. We also found no evidence of polymorphic repeat sequence. Characteristics of this family are: second to 5 finger flexor deformity and joint fusion, lateral phalanx, third metacarpal and proximal phalanx bone fusion, mild clinical phenotype and more severe clinical phenotype that coexist. A study on the expansion of the phenotype of HOXD13 gene PAE mutation spectrum, providing more information for polyalanine repeat polymorphism in nature. In addition, the unique clinical phenotype of this family also allows us to have a further understanding of SPD.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R394.3

【引证文献】