本文關(guān)鍵詞：HOXD13基因多聚丙氨酸延展突變致一獨(dú)特臨床表現(xiàn)的并指（趾）多指（趾）家系　出處：《吉林大學(xué)》2011年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： SPD HOXD13 PAE 突變分析

【摘要】：并指(趾)多指(趾)畸形(SPD)是HOXD13基因多聚丙氨酸延展突變引起的以常染色體顯性遺傳為特點(diǎn)的先天性肢體畸形。SPD典型的臨床表現(xiàn)為,手部第3/4指并指,足部第4/5趾并趾。表型較重者可出現(xiàn)手部第4指復(fù)指和足部第4趾復(fù)指,癥狀極嚴(yán)重的SPD病例還會(huì)出現(xiàn)尿道下裂。三種遺傳上不同的SPD位點(diǎn)已經(jīng)被確定,分別為SPD1、SPD3和SPD3。 HOX基因編碼一個(gè)轉(zhuǎn)錄因子超家族,很多研究證實(shí),HOX基因在胚胎發(fā)育過(guò)程中起著重要的作用。HOX基因共有HOXA、HOXB、HOXC、HOXD四個(gè)基因簇,分別位于不同的染色體上。HOXD13位于HOXD簇最5′端,有兩個(gè)外顯子,其中外顯子1包含一個(gè)不完全的三核苷酸重復(fù)序列,編碼一個(gè)由15個(gè)丙氨酸殘基組成的多聚丙氨酸片段。多聚丙氨酸鏈延展突變可導(dǎo)致SPD1,很多研究都認(rèn)為少于6個(gè)丙氨酸插入不能引起臨床表現(xiàn),是沒(méi)有致病性的。 我們調(diào)查了一個(gè)三代的中國(guó)家系,其中受影響的3個(gè)個(gè)體表現(xiàn)為三種變易的手足畸形。我們對(duì)該家系進(jìn)行詳細(xì)的資料收集整理。對(duì)3名患者進(jìn)行詳細(xì)的臨床查體,并對(duì)患者的雙手雙腳拍攝數(shù)碼照片和X線片。在獲得知情同意后,抽取患者及直系親屬外周血樣,對(duì)先證者進(jìn)行核型分析,并從患者、患者直系親屬及100名對(duì)照志愿者外周抗凝血中提取DNA。-20度儲(chǔ)存?zhèn)溆?設(shè)計(jì)引物對(duì)HOXD13兩外顯子進(jìn)行PCR,產(chǎn)物送生物公司測(cè)序。 最終核型分析結(jié)果顯示,未發(fā)現(xiàn)染色體結(jié)構(gòu)和數(shù)目的異常。家系中所有三名受影響個(gè)人的HOXD13基因第1外顯子多聚丙氨酸鏈區(qū)域插入了27bp的三核苷酸重復(fù)突變(c. 186- 212dup)。此種突變未出現(xiàn)在家系中所有未受影響個(gè)人及無(wú)關(guān)對(duì)照個(gè)體。在對(duì)照組中我們也沒(méi)有發(fā)現(xiàn)重復(fù)序列的多態(tài)性證據(jù)。此家系的特點(diǎn)為:第2到5指的屈指畸形和關(guān)節(jié)融合、橫向指骨、第三掌骨和近節(jié)指骨的骨融合,輕微的臨床表型和更為嚴(yán)重的臨床表型共存。這項(xiàng)研究擴(kuò)展了HOXD13基因PAE突變的表型譜,為多聚丙氨酸重復(fù)序列多態(tài)性本質(zhì)提供了更多的信息。另外,此家系獨(dú)特的臨床表型也使我們對(duì)SPD有了進(jìn)一步的認(rèn)識(shí)。
[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.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R394.3

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 李柯;ENU誘變獲得一種多趾小鼠及其突變基因的鑒定[D];揚(yáng)州大學(xué);2012年

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本文編號(hào)：1420670