本文選題：腦橋小腦發(fā)育不全 + 全外顯子組測(cè)序��； 參考：《安徽醫(yī)科大學(xué)》2016年碩士論文

【摘要】：研究背景腦橋小腦發(fā)育不全(Pontocerebellar Hypoplasia,PCH)是一組少見(jiàn)的常染色體隱性遺傳的神經(jīng)系統(tǒng)變性疾病,通常在出生前發(fā)病。其共同特征包括腦橋、小腦發(fā)育不全、萎縮,進(jìn)行性加重的小頭畸形和不同程度的腦室擴(kuò)大,有時(shí)大腦也可受累[1]。其臨床癥狀可表現(xiàn)為嚴(yán)重的認(rèn)知障礙,運(yùn)動(dòng)障礙以及癲癇發(fā)作。目前該疾病可分為8種亞型,針對(duì)不同亞型的致病機(jī)制也有所報(bào)。對(duì)PCH的治療措施有限,僅以支持治療為主,且預(yù)后較差。目的通過(guò)對(duì)一個(gè)腦橋小腦發(fā)育不全(PCH)家系研究,進(jìn)一步了解并探討PCH的臨床特點(diǎn)及致病基因,為該疾病的診斷、預(yù)后評(píng)估提供依據(jù)。方法收集一個(gè)腦橋小腦發(fā)育不全的家系成員(先證者、先證者弟弟、先證者父親、先證者母親)的臨床資料,了解該家系的發(fā)病情況及臨床特點(diǎn),同時(shí)進(jìn)行詳細(xì)的神經(jīng)系統(tǒng)的檢查及腦電、頭顱MRI檢查;應(yīng)用簡(jiǎn)易智能精神狀態(tài)檢查量表(mini-mental stateexamination,MMSE)、蒙特利爾認(rèn)知評(píng)估量表(Montreal Cognitive Assessment,Mo CA)對(duì)家系成員進(jìn)行評(píng)分、并繪制系譜圖、進(jìn)行腦電、頭顱磁共振檢查,征得該家系成員知情同意,采集其中4名家系成員外周靜脈血各4ml,進(jìn)行全外顯子組測(cè)序分析(數(shù)據(jù)分析模式僅限于孟德?tīng)栠z傳病),在驗(yàn)證已知相關(guān)突變基因的基礎(chǔ)上,進(jìn)一步篩選出未知相關(guān)突變基因,并對(duì)其進(jìn)行Sanger測(cè)序驗(yàn)證;以進(jìn)一步完善本家系疾患的基因普并支持其診斷。結(jié)果(1)該家系成員無(wú)三代以內(nèi)近親婚姻的情況,家系中除先證者及其弟弟,其他成員沒(méi)有類(lèi)似疾患發(fā)生。先證者及其弟弟發(fā)病年齡,發(fā)病癥狀幾乎一致,神經(jīng)系統(tǒng)檢查結(jié)果相似,如3歲左右癲癇發(fā)作,認(rèn)知障礙,走直線不穩(wěn),肌張力低下,腱反射消失;(2)腦電圖顯示各導(dǎo)聯(lián)棘波發(fā)放;(3)頭顱MRI顯示小腦,腦干不同程度的發(fā)育不良。(4)神經(jīng)心理學(xué)量表:先證者:Mo Ca評(píng)分4分,MMSE評(píng)分8分;先證者弟弟:Mo Ca評(píng)分21分,MMSE評(píng)分22分;先證者父親:Mo Ca評(píng)分24分,MMSE評(píng)分30分;先證者母親:Mo Ca評(píng)分28分,MMSE評(píng)分29分;(4)全外顯子組測(cè)序發(fā)現(xiàn)了1個(gè)突變,是否和該家系疾病有關(guān),有待進(jìn)一步研究。結(jié)論(1)本研究未發(fā)現(xiàn)該疾病已知的相關(guān)基突變因;(2)未篩選出臨床表型與遺傳方式相匹配的突變基因作Sanger測(cè)序;(3)發(fā)現(xiàn)了1個(gè)基因突變,符合常染色隱性遺傳,但是否與該疾病相關(guān),有待進(jìn)一步研究。
[Abstract]:Background Pontocerebellar Hypoplasia (PCH) is a rare group of autosomal recessive neurodegenerative diseases usually occurring before birth. Common features include pons, cerebellar dysplasia, atrophy, progressive microcephaly and varying degrees of ventricular enlargement, sometimes involving the brain [1]. Its clinical symptoms can be characterized by severe cognitive impairment, motor disorder and seizures. At present, the disease can be divided into 8 subtypes, and the pathogenesis of different subtypes is also reported. The treatment of PCH is limited, only supportive treatment, and poor prognosis. Objective to study a pedigree of pons cerebellar dysplasia (pons) and to explore the clinical features and pathogenic genes of PCH in order to provide evidence for the diagnosis and prognosis evaluation of the disease. Methods the clinical data of a family member (proband, proband brother, proband father, proband mother) with cerebellopontine dysplasia were collected to find out the incidence and clinical characteristics of the pedigree. At the same time, a detailed examination of the nervous system, EEG and MRI were performed, and the mini-mental state examination scale (MMSE), the Montreal Cognitive Assessment scale (MMSE) and the Montreal Cognitive Assessment scale (MMSE) were used to evaluate the family members and draw pedigree diagrams for EEG. Cranial magnetic resonance imaging, with the informed consent of the member of the family, The peripheral venous blood of 4 family members were collected and sequenced in the whole exon group. (the data analysis model was limited to Mendelian disease. Based on the verification of known mutation genes, unknown mutation genes were further screened. Sanger sequencing was performed to further improve the gene expression of the disease and to support the diagnosis of the disease. Results 1) the family members had no close relatives within three generations, except the proband and their younger brother, there were no similar diseases in the family. The proband and his younger brother had almost the same onset age, almost identical symptoms, and similar neurological examination results, such as seizures about 3 years old, cognitive disorders, straight line instability, and hypotonia. MRI showed cerebellum and brainstem dysplasia in different degrees. Neuropsychological scale: proband: proband 4: Mo score 4 and MMSE score 8; The proband's younger brother: Mo Ca score 21 points and MMSE score 22 points; proband father: Mo Ca score 24 points and MMSE score 30 points; proband mother: Mo Ca score 28 points; MMSE score 29 points;) Total exon group sequencing found a mutation, whether it is related to the family disease. Further study is needed. Conclusion 1) in this study, we did not find a known cause of the associated mutation of the disease. (2) A mutation gene matching clinical phenotypic and genetic pattern was not screened for Sanger sequencing. (3) A gene mutation was found, which was consistent with the recessive heredity of normal staining. But whether or not it is related to the disease needs further study.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R742

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 李隱存,嚴(yán)穎熙;典型腦發(fā)育不全綜合征:通過(guò)面部看腦發(fā)育[J];國(guó)外醫(yī)學(xué).遺傳學(xué)分冊(cè);2000年01期

2 鄭錦銀;小兒腦發(fā)育不全23例誤診分析[J];臨床醫(yī)學(xué);2002年06期

3 劉愉;李秀娟;鄧林菲;唐麗君;;長(zhǎng)春地區(qū)先天腦發(fā)育不全患兒的染色體核型分析[J];中國(guó)優(yōu)生與遺傳雜志;2006年07期

4 于海平;;中西醫(yī)結(jié)合治療大腦發(fā)育不全的療效觀察[J];河南中醫(yī)學(xué)院學(xué)報(bào);1976年01期

5 ;新針治療先天性腦發(fā)育不全一例報(bào)告[J];新醫(yī)學(xué);1972年06期

6 ;中醫(yī)治療小兒大腦發(fā)育不全一例報(bào)告[J];天津醫(yī)藥;1974年09期

7 尹宗信;;靈芝治療腦發(fā)育不全60例臨床分析[J];安徽醫(yī)學(xué);1977年01期

8 肖鎮(zhèn)祥;;大腦發(fā)育不全的診斷和治療[J];中級(jí)醫(yī)刊;1979年04期

9 馬沛然,吳韻明;70例腦發(fā)育不全患兒甲狀腺功能觀察小結(jié)[J];山東醫(yī)藥;1980年01期

10 鄭光明;李仁俊;;復(fù)方狗腦注射液治療小兒腦發(fā)育不全的療效研究[J];中成藥研究;1980年01期

相關(guān)會(huì)議論文 前2條

1 何玉海;于海波;;從脾胃論治小兒腦發(fā)育不全[A];2011中國(guó)針灸學(xué)會(huì)年會(huì)論文集（摘要）[C];2011年

2 何玉海;于海波;;從脾胃論治小兒腦發(fā)育不全[A];廣東省針灸學(xué)會(huì)第十二次學(xué)術(shù)研討會(huì)暨全國(guó)腦卒中及脊柱相關(guān)性疾病非藥物診療技術(shù)培訓(xùn)班論文集[C];2011年

相關(guān)重要報(bào)紙文章 前4條

1 廣州空軍醫(yī)院神經(jīng)外科主任醫(yī)師 唐運(yùn)林;某些大腦發(fā)育不全也可手術(shù)治療[N];家庭醫(yī)生報(bào);2003年

2 黃蘇榕;中科院上海神經(jīng)所發(fā)現(xiàn)中、小腦發(fā)育不全分子機(jī)制[N];中國(guó)醫(yī)藥報(bào);2007年

3 記者 黃劍釗 通訊員 聶長(zhǎng)江 唐運(yùn)林;微創(chuàng)手術(shù)成功拯救癡呆兒[N];廣東科技報(bào);2004年

4 洪秀;嬰幼兒驚厥的應(yīng)急處理[N];民族醫(yī)藥報(bào);2002年

相關(guān)碩士學(xué)位論文 前1條

1 潘晴晴;一個(gè)罕見(jiàn)腦橋小腦發(fā)育不全家系臨床研究及遺傳學(xué)分析[D];安徽醫(yī)科大學(xué);2016年

，

本文編號(hào)：1974880