本文關(guān)鍵詞： 眼-耳-脊柱發(fā)育不良 小耳畸形 MSX1 MSX2 孕期危險因素　出處：《復(fù)旦大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的本研究通過文獻回顧,比較我院眼-耳-脊柱發(fā)育不良(oculo-auriculo-vertebral spectrum, OAVS)病例與國外病例臨床特征的相同點與不同點；應(yīng)用單因素卡方分析和logistic多因素回歸分析的方法比較患者組與對照組母親孕期情況的差異,以找到與OAVS相關(guān)的孕期高危因素,為產(chǎn)前預(yù)防提供思路；本研究應(yīng)用PCR擴增目的DNA序列并直接測序的方法對OAVS患者血基因組MSX1、MSX2基因外顯子突變進行檢測,以了解該畸形與這兩個基因外顯子突變的關(guān)系,為進一步研究發(fā)病機制確定方向。 方法本文收集了從2007.9到2009.7到我院門診咨詢或住院進行耳廓再造及聽力重建術(shù)的208名眼-耳-脊柱發(fā)育不良患者。入選標(biāo)準(zhǔn)：患者有單／雙側(cè)耳廓畸形或附耳伴同側(cè)半面短小；雙側(cè)受累定義為耳廓畸形、附耳或耳前瘺管在雙側(cè)出現(xiàn)；親屬中有耳廓畸形、附耳或瘺管的患者被定義為有家族史,其余為散發(fā)病例。根據(jù)國內(nèi)外對先天性耳廓畸形和OAVS的相關(guān)研究,本研究制定了詳細的《臨床資料表》和《孕期危險因素調(diào)查表》。對于208例患者的臨床資料,本研究與國外16篇文獻比較了OAVS十項主要臨床特征的百分比。208例患者中,有179例患兒母親完成了《孕期危險因素調(diào)查表》,本研究選取患兒年齡在3-14歲的病例118例,并同時調(diào)查了118例3-14歲正常兒童母親孕期情況作為對照組,使用SPSS 13.0統(tǒng)計軟件,用卡方分析法對高齡產(chǎn)婦(35歲)、自然流產(chǎn)史、早孕感染、早孕用藥史、早孕先兆流產(chǎn)史、早孕毒物接觸史等16個變量進行了單因素卡方分析,挑選出有意義的因素后,再用logistic多因素回歸法進行分析。此外,應(yīng)用收集的124例患者血樣,抽提出DNA后用PCR擴增了MSX1、MSX2基因外顯子序列并直接測序,用Mutation Surveyor軟件分析測序結(jié)果。 結(jié)果 1.208例患者年齡在3月到31歲之間。69.7%的患者為男性；10.1%的患者有家族史,其余為散發(fā)病例；65.4%的患者單側(cè)受累,單側(cè)中56.6%為右側(cè)受累；98.6%的患者伴發(fā)外耳道閉鎖或狹窄；僅有14.4%的患者伴發(fā)附耳或耳前瘺管；28.4%的病例伴發(fā)耳畸形同側(cè)或雙側(cè)下頜骨發(fā)育不良；4.3%的病例有不同眼部缺陷；只有2例患者確診脊柱畸形,1例有先天性室間隔缺損。除了伴發(fā)外耳道閉鎖或狹窄百分比明顯高于國外報道,大部分結(jié)果與國外報道相似。 2.患者組和對照組在早孕接觸有毒物質(zhì)、孕期貧血、早孕感染、早孕用藥史這4個方面差異有統(tǒng)計學(xué)意義(P0.05),可能為OAVS的孕期危險因素。其中早孕接觸有毒物質(zhì)的OR值最大,為9.847,說明母親孕期接觸油漆、化工原料等與OAVS的相關(guān)性很大。 3.在124例患者當(dāng)中,發(fā)現(xiàn)1例患者MSX1基因第二個外顯子上出現(xiàn)3473GGT突變,為無義突變,編碼氨基酸仍為亮氨酸,此突變在100例正常人中驗證均未發(fā)現(xiàn)異常。本研究未發(fā)現(xiàn)MSX2基因外顯子突變,但發(fā)現(xiàn)MSXl,MSX2基因6個已報道過的SNP。 結(jié)論本組OAVS患者臨床特征與國外病例相似�；颊吣赣H孕期貧血、早孕感染、早孕用藥和早孕接觸有毒物質(zhì)等環(huán)境因素可能與發(fā)病相關(guān)。此先天性畸形由MSX1,MSX2基因外顯子突變直接引起的可能性能不大。然而,有典型家族史的病例應(yīng)該存在遺傳學(xué)上的變異,需進一步進行分子生物學(xué)研究。
[Abstract]:The purpose of this study through the literature review, comparison of our hospital oculo ariculo vertebral dysplasia (oculo-auriculo-vertebral spectrum OAVS) common clinical features in the patients with foreign cases and different points; difference method using univariate chi square analysis and logistic regression analysis between patient group and control group pregnant condition, high risk pregnancy in order to find the factors associated with OAVS, to provide ideas for prenatal prevention; amplified target DNA sequence and direct sequencing of the research on the application of PCR in blood of patients with OAVS genomic MSX1, MSX2 gene exon mutations were detected, in order to understand the deformity and the two exon mutation relationship, determine the direction for the study of pathogenesis the mechanism further.
Methods from 2007.9 to 2009.7 in our hospital outpatient consultation or hospitalization for auricle reconstruction and reconstruction of hearing in 208 eyes - ears - spine dysplasia patients. Inclusion criteria: Patients with single / bilateral ear malformation or ear with ipsilateral hemifacial microsomia; bilateral involvement is defined as the auricle malformation, ear or ear fistula in bilateral relatives; auricle deformity, ear or fistula patients were defined as having family history, the rest were sporadic. According to the related research on congenital auricular deformities and OAVS at home and abroad, this study developed a detailed table > and < < clinical pregnancy risk factors for the clinical data of 208 questionnaires. Patients in this study, with 16 foreign literatures and comparison of the OAVS ten main clinical features of the percentage of.208 patients, 179 patients completed the "mother's pregnancy risk factors questionnaire", this study selected children in At the age of 3-14 years old in 118 cases, and also investigated the 118 cases of 3-14 years old children with normal pregnancy as control group, using SPSS 13 statistical software, advanced maternal age on using chi square analysis (35 years old), the history of spontaneous abortion in early pregnancy, infection, pregnancy medication history, pregnancy history of early pregnancy threatened abortion, poison contact history 16 variables are single factor chi square analysis, select significant factors, analysis and multiple factor Logistic regression method. In addition, 124 cases of patients with blood samples collected using, extracted after DNA was amplified by PCR MSX1 and MSX2 gene exon sequences and direct sequencing, sequencing and analysis of results using Mutation Surveyor software.
Result
1.208 patients at the age of.69.7% from March to 31 between the ages of the patients were male; 10.1% of patients have family history, for the rest of 65.4% sporadic cases; patients with unilateral involvement, 56.6% unilateral right hair involvement; external auditory canal atresia or stenosis and 98.6% patients with ear hair or preauricular fistula; only 14.4% of the patients; 28.4% of the patients with microtia ipsilateral or bilateral mandibular dysplasia; 4.3% cases with different eye defects; only 2 cases were diagnosed as spinal deformity, 1 cases with congenital ventricular septal defect. In addition to aural atresia or stenosis was significantly higher than that reported abroad, most similar to the results reported abroad.
2. patients group and control group exposed to the toxic substances in early pregnancy anemia during pregnancy, early pregnancy infection, there were statistically significant differences in early pregnancy medication history of these 4 aspects (P0.05), may be the risk factors during pregnancy OAVS. The early exposure to toxic substances and the OR value is 9.847, that maternal exposure to chemical raw materials such as paint, correlation with OAVS a lot.
3. of the 124 patients, 1 patients found that second of the MSX1 gene exon 3473GGT mutation, nonsense mutation, encoding amino acids are leucine, this mutation in 100 cases of normal people in verification were not unusual. This study found no mutations of exons of MSX2 gene, but the MSXl. 6 MSX2 genes have been reported SNP.
Conclusion the clinical characteristic of OAVS patients with foreign similar cases. Patients with maternal anemia during pregnancy, early pregnancy infection, pregnancy and early pregnancy medication exposure to environmental factors of toxic and hazardous substances may be correlated with the incidence of congenital malformation. This consists of MSX1, MSX2 gene mutation in exon may be directly caused by the performance little. However, some typical cases of family history should be there is variation in genetics, the further research of molecular biology.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R764

【參考文獻】

相關(guān)期刊論文 前3條

1 蔣文杰,裴開顏,李文軍,施立海,趙延勇,莊洪興;小耳畸形綜合征病因的初步調(diào)查[J];生殖醫(yī)學(xué)雜志;2004年01期

2 朱軍,王艷萍,梁娟,周光萱;1988～1992年全國先天性無耳和小耳畸形發(fā)病率的抽樣調(diào)查[J];中華耳鼻咽喉科雜志;2000年01期

3 杜佳梅;郭萬厚;韓娟;莊洪興;;先天性小耳畸形危險因素的病例對照研究[J];中華耳鼻咽喉頭頸外科雜志;2006年02期

，

本文編號：1451759