本文選題：先天性眼外肌纖維化　切入點(diǎn)：KIF21A　出處：《青島大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的收集1中國(guó)先天性眼外肌纖維化綜合征(Congenital fibrosis of the extraocular muscles, CFEOM)家系與7例散發(fā)病例,分析其臨床表型和遺傳特點(diǎn),研究在該家系及散發(fā)病例中是否存在已知的致病基因KIF21A、PHOX2A/ARIX, TUBB3, TUBB2B的已知突變位點(diǎn)的突變,探討不同人種中CFEOM家系及散發(fā)病例的遺傳異質(zhì)性。 方法收集青島大學(xué)附屬醫(yī)院確診的1CFEOM家系(家系JN)2代4人及散發(fā)病例7例。對(duì)家系所有成員及散發(fā)病例進(jìn)行詳細(xì)眼科檢查及斜視�？茩z查,進(jìn)行臨床表型分析。利用聚合酶鏈反應(yīng)擴(kuò)增已知的致病基因KIF21A、PHOX2A/ARIX、TUBB3、TUBB2B已知突變的外顯子區(qū)域,對(duì)擴(kuò)增產(chǎn)物進(jìn)行測(cè)序分析,篩查是否存在已知熱點(diǎn)的突變。對(duì)照組隨機(jī)選取100名健康中國(guó)人,且無血緣關(guān)系。 結(jié)果1.臨床研究：本研究中CFEOM家系的患者為母子關(guān)系,均伴有雙眼先天性上瞼下垂,眼球運(yùn)動(dòng)受限,被動(dòng)牽拉實(shí)驗(yàn)(+),及代償頭位。散發(fā)患者7例,男性5例,女性2例,其中3例固定于內(nèi)斜位,2例伴有異常神經(jīng)支配其中1例伴有下頜瞬目綜合征。2.在家系JN的2例患者中均發(fā)現(xiàn)KIF21A基因2860CT錯(cuò)義突變,該家系中的正常者及正常對(duì)照組均不存在該突變。散發(fā)的7例患者在已知的候選基因KIF21A、 PHOX2A/ARIX、TUBB3、TUBB2B的已知突變位點(diǎn)處均未發(fā)現(xiàn)致病性突變。 結(jié)論1.臨床表型特征：根據(jù)臨床表型及遺傳學(xué)特點(diǎn),家系JN為CFEOM1型家系。7例散發(fā)患者具有不同臨床表型,其中CFEOM1型1例,CFEOM2型1例,CFEOM3型5例,均不伴有其他全身系統(tǒng)性疾病。2.遺傳學(xué)特征：家系JN屬于常染色體顯性遺傳,臨床表型由KIF21A基因的第21外顯子2860CT錯(cuò)義突變導(dǎo)致,KIF21A基因?yàn)樵摷蚁档闹虏』�。�?duì)本研究中的7例散發(fā)患者KIF21A、PHOX2A/ARIX、TUBB3、TUBB2B已知突變位點(diǎn)的篩查,未發(fā)現(xiàn)已報(bào)道的熱點(diǎn)突變,提示該7例散發(fā)CFEOM患者的致病位點(diǎn)與已報(bào)道的國(guó)外人種中散發(fā)的熱點(diǎn)突變不同,說明該疾病具有遺傳異質(zhì)性。
[Abstract]:Objective to investigate the phenotypic and genetic characteristics of congenital extraocular muscle fibrosis syndrome (CFEOM) in 7 sporadic Chinese patients with congenital extraocular muscle fibrosis syndrome (CFEOM). To study the mutation of known mutation sites of KIF21A PHOX2A / ARIX, TUBB3, TUBB2B in this family and sporadic cases, and to explore the genetic heterogeneity of CFEOM pedigree and sporadic cases in different ethnic groups. Methods one CFEOM pedigree (4 cases of JN)2 generation and 7 cases of sporadic cases) confirmed in the affiliated Hospital of Qingdao University was collected. All the family members and sporadic cases were examined by detailed ophthalmologic examination and strabismus examination. The exon region of known pathogenic gene PHOX2A / ARIXTUBB3TUBB2B was amplified by polymerase chain reaction (PCR), and the amplified products were sequenced. In the control group, 100 healthy Chinese were randomly selected and were not related to each other. Clinical study: in this study, the patients of CFEOM family were related to mother and child, with congenital ptosis of both eyes, limited eyeball movement, passive traction test (ptosis, and compensatory head position). There were 7 sporadic patients, 5 males and 2 females. Among them, 3 cases were fixed in the internal oblique position, 2 cases were accompanied with abnormal nerve innervation, and 1 case was accompanied by mandibular blink syndrome .2.The missense mutation of KIF21A gene 2860CT was found in 2 cases of JN. The mutation was not found in normal subjects and normal controls. No pathogenicity mutations were found in the known candidate gene KIF21A, PHOX2A / ARIXTUBB3TUBB2B. Clinical phenotypic characteristics: according to the clinical phenotypic and genetic characteristics, there were 7 cases of sporadic CFEOM1 family with different phenotypes in JN pedigree, including 1 case of CFEOM1 type and 1 case of CFE OM2 type 1 case of CFEOM3 type. Genetic characteristics: family JN belongs to autosomal dominant inheritance. The clinical phenotype was caused by missense mutation in exon 21 of KIF21A gene, which resulted in KIF21A gene being the pathogenic gene in this pedigree. In this study, no reported hot spot mutations were found in 7 sporadic patients with known mutation sites of KIF21A / ARIXT TUBB3TUBB3TUBB2B. The results suggest that the pathogenicity of the 7 sporadic CFEOM patients is different from that of the reported hot spot mutations in foreign ethnic groups, indicating that the disease is genetically heterogeneous.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R777.4

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相關(guān)期刊論文 前2條

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本文編號(hào)：1607415