本文選題：腦性癱瘓 + KANK1�。� 參考：《佳木斯大學(xué)》2017年碩士論文

【摘要】：目的:檢測我國先天性腦性癱瘓(簡稱腦癱)兒童KANK1、GAD1和AP4復(fù)合物(包括AP4E1、AP4B1、AP4M1和AP4S1)基因突變的狀況,初步探討其基因型與臨床表型的關(guān)系,探尋先天性腦癱的病因,為腦癱的預(yù)防及早期診斷探索新的方法。方法:選擇在黑龍江省小兒腦性癱瘓防治療育中心、河南中醫(yī)藥大學(xué)第一附屬醫(yī)院、安徽醫(yī)科大學(xué)第一附屬醫(yī)院、深圳市兒童醫(yī)院、西安中醫(yī)腦病醫(yī)院等院就診的1-12歲先天性腦癱兒童149例。對腦癱兒童進行全面臨床評估,詳細收集病史等臨床資料,采集患兒、父母和(或)其同胞的外周靜脈血,提取DNA,運用高通量測序技術(shù)對KANK1、GAD1和AP4復(fù)合物基因進行DNA檢測,并對發(fā)現(xiàn)的變異進行Sanger測序驗證。結(jié)果:149例腦癱男女比例為1.87:1(男97例,女52例),均為足月出生,無明顯高危因素。腦癱類型分布由高到低依次為痙攣型雙癱48例(32.21%),混合型27例(18.12%),痙攣型四肢癱26例(17.45%),痙攣型偏癱25例(16.78%),不隨意運動型20例(13.42%),共濟失調(diào)型3例(2.01%);其中痙攣型最多,共99例(66.44%)。149例腦癱合并癥前五位為:智力落后、語言障礙、小頭畸形、視覺功能障礙和癲癇。經(jīng)二代測序及Sanger驗證,共發(fā)現(xiàn)6個致病性基因突變,涉及6例患兒(4%),受累基因為KANK1和AP4S1。攜帶基因突變的腦癱兒童均為男性,均無腦癱家族史。其中,2例合并智力落后、語言功能障礙、小頭畸形的痙攣型雙癱的同胞患兒,攜帶KANK1基因的插入突變(c.1274_1275ins AGCTGT,p.427_428ins Ala Val);1例合并智力落后、雙眼內(nèi)斜視、語言障礙、小頭畸形、行為異常和孤獨癥譜系障礙的痙攣型四肢癱患兒,攜帶KANK1基因的錯義突變(c.2167CT、p.Arg723Cys);1例無合并癥的痙攣型偏癱患兒,攜帶KANK1基因的錯義突變(c.3482AG,p.Asn1161Ser);1例合并智力落后、語言發(fā)育遲緩和小頭畸形的痙攣型四肢癱患兒,攜帶KANK1基因的錯義突變(c.2110GA,p.Asp704Asn);1例合并智力落后、語言障礙、小頭畸形和癲癇的痙攣型四肢癱患兒,攜帶KANK1基因的缺失突變(c.3103_3105del,p.1039del)和AP4S1基因的無義突變(c.289CT,p.Arg97Ter)。以上突變均來源于患兒父親,AP4S1基因為常染色體隱性遺傳,KANK1基因的遺傳方式尚不明確。除AP4S1基因的無義突變有報道外,其它突變均為首次報道。攜帶致病基因突變的患者中伴發(fā)小頭畸形(83%)的比例較未攜帶突變的患者(16%)高,差異具有統(tǒng)計學(xué)意義(P0.05)。結(jié)論:1.KANK1和AP4S1基因突變是中國腦癱兒童的致病因素之一;2.KANK1和AP4S1基因突變可導(dǎo)致痙攣型腦癱;3.KANK1和AP4S1基因突變所致腦癱更易伴有小頭畸形;4.腦癱兒童的KANK1基因突變均來源于其父親;5.KANK1基因突變的臨床表型存在變異。
[Abstract]:Objective: to detect the gene mutations of KANK1T GAD1 and AP4 complex (including AP4E1AP-4B1A1AP4M1 and AP4S1) in children with congenital cerebral palsy (CP) in China, and to explore the relationship between genotypes and clinical phenotypes, and to explore the etiology of congenital cerebral palsy. To explore a new method for the prevention and early diagnosis of cerebral palsy. Methods: the first affiliated Hospital of Henan University of traditional Chinese Medicine, the first affiliated Hospital of Anhui Medical University, and the Children's Hospital of Shenzhen City were selected. 149 cases of congenital cerebral palsy children aged 1-12 years in Xi'an Encephalopathy Hospital. The clinical data of children with cerebral palsy were evaluated, the clinical data such as history were collected in detail, the peripheral venous blood of children, parents and / or their sibling were collected, the DNA was extracted, and the DNA of KANK1 + GAD1 and AP4 complex genes were detected by high-throughput sequencing technique. The mutation was sequenced by Sanger. Results the ratio of male to female in 149 cases of cerebral palsy was 1.87: 1 (97 males and 52 females). The distribution of cerebral palsy from high to low were spastic diplegia in 48 cases (32.21%), mixed type in 27 cases (18.12%), spastic tetraplegia in 26 cases (17.45%), spastic hemiplegia in 25 cases (16.78%), involuntary motor type in 20 cases (13.42%), ataxia type in 3 cases (2.01%). A total of 99 cases (66.44%). 149 cases of cerebral palsy complicated by the first five: mental retardation, language disorders, microcephaly, visual dysfunction and epilepsy. Six pathogenicity gene mutations were identified by second generation sequencing and Sanger analysis, involving 6 children (4%), involving KANK1 and AP4S1. All the children with cerebral palsy with gene mutation were male and had no family history of cerebral palsy. Among them, 2 children with mental retardation, language dysfunction, spastic diplegia with microcephaly, 1 case with mental retardation, binocular esotropia, language disorder, microcephaly, and microcephaly were accompanied by c.1274_1275ins AGCT GTP.427428ins Ala Val. In children with spastic quadriplegia with abnormal behavior and autism spectrum disorder, the missense mutation of KANK1 gene (c. 2167CTP. Arg723Cys) and the missense mutation of KANK1 gene (c. 3482AGp.Asn1161Ser) combined with mental retardation were found in one child with spastic hemiplegia without complication. Children with spastic quadriplegia with language retardation and microcephaly, one patient with kANK1 gene missense mutation (c.2110GAp.Asp704Asn), one child with mental retardation, language disorder, microcephaly and epilepsy spastic quadriplegia. The deletion mutation of KANK1 gene (c. 3105 delp. 1039del) and the nonsense mutation of AP4S1 gene (c. 289 CTP. Arg97Ter). All of the above mutations originated from the father of the child, AP4S1 because the genetic pattern of the autosomal recessive gene KANK1 was not clear. Except for the reported nonsense mutation of AP4 S1 gene, all other mutations were reported for the first time. The proportion of microcephaly with microcephaly (83%) was higher in patients with pathogenic gene mutation than that in patients without mutation (16%), the difference was statistically significant (P0.05). Conclusion 1. The mutation of KANK1 and AP4S1 gene is one of the pathogenic factors of cerebral palsy in Chinese children. Secondly, the mutation of KANK1 and AP4S1 gene may lead to spastic cerebral palsy. 3. The mutation of KANK1 and AP4S1 gene is more likely to cause cerebral palsy associated with microcephaly. KANK1 gene mutations in children with cerebral palsy all originated from the clinical phenotypic variation of KANK1 gene mutations.
【學(xué)位授予單位】：佳木斯大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R742.3

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相關(guān)期刊論文 前1條

1 李曉捷;唐久來;馬丙祥;秦炯;鄒麗萍;王家勤;;腦性癱瘓的定義、診斷標(biāo)準(zhǔn)及臨床分型[J];中華實用兒科臨床雜志;2014年19期

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本文編號：2097284