本文選題：遺傳性少毛癥 + 單純性頭皮性少癥　； 參考：《安徽醫(yī)科大學》2017年碩士論文

【摘要】：研究背景遺傳性少毛癥是表現(xiàn)為毛發(fā)持續(xù)性缺失的單基因遺傳性皮膚病,此類疾病具有顯著的臨床特點和遺傳分型。臨床表現(xiàn):患者表現(xiàn)為新生兒時期、嬰幼兒時期開始出現(xiàn)毛發(fā)的脫落,少數(shù)患者表現(xiàn)為青春期時發(fā)病�；颊叩拿济⒔廾�、陰毛、腋毛等均可受累或正常。根據(jù)遺傳性少毛癥的臨床特點大致可以分為以下5種類型:1.遺傳性單純性頭皮性少毛癥;2.遺傳性單純性少毛癥;3.Marie Unna型少毛癥;4.常染色體顯性羊毛狀發(fā);5.生長期毛發(fā)松動綜合征等。隨著分子遺傳學的發(fā)展,這些先天性少毛癥的致病基因也都陸續(xù)的被報道,而我們此次研究則主要是針對遺傳性單純性頭皮性少毛癥的致病基因CDSN基因的直接測序,檢測CDSN基因的突變位點。研究目的確定遺傳性單純性頭皮性少毛癥大家系致病的一個新的致病突變,從分子遺傳學水平闡述其發(fā)病機制,并為以后的遺傳咨詢,基因診斷,提供理論依據(jù),豐富遺傳性少毛癥遺傳突變譜。實驗材料與方法對一例遺傳性單純性頭皮性少毛癥家系成員進行遺傳學調查、實驗室檢查、臨床表現(xiàn)及體征的檢查;2.經(jīng)病人知情允許后拔取患者的病發(fā)若干進行電鏡掃描分析,采集靜脈外周全血樣本并提取DNA樣本;3.用premier 5.0對既往報道過得CDSN基因進行引物設計;4.采用PCR擴增技術,擴增患者及家族內其他成員的CDSN基因的外顯子;5.應用ABI3730XL測序儀進行直接測序,確定有無致病性突變;6.根據(jù)突變是否符合家系內遺傳規(guī)律對測序數(shù)據(jù)進行分析;7.總結國內外文獻報道,探討突變位點與表型之間的關系。結果該家系患者均表現(xiàn)為青春期時出現(xiàn)頭皮油脂分泌增加,頭發(fā)逐漸脫落、稀疏、細軟,長到7cm左右不再生長。陰毛、腋毛,眉毛、睫毛,牙齒、指甲等均未受累。體格檢查:神清精神可,身體及智力發(fā)育未見異常。病發(fā)在肖特基場發(fā)射高分辨電鏡掃描顯示:毛發(fā)正常。DNA測序結果顯示,家系內所有的患者的均出現(xiàn)一個編碼區(qū)的插入突變(c.520_521ins G),所有家系內正�；颊呔窗l(fā)現(xiàn)該插入突變,(3)基因型與表型之間的相關性研究顯示,編碼區(qū)的插入突變(c.520ins G)導致了下游的框移突變,使后續(xù)的氨基酸結構發(fā)生改變從而引起表型的改變。結論對一個中國遺傳性單純性頭皮性少毛癥家系,進行CDSN基因直接測序,測序結果分析,發(fā)現(xiàn)一個插入突變c.520_521ins G(P.A174fs)。
[Abstract]:Background hereditary hypotrichoresis is a single gene inherited dermatosis characterized by persistent hair loss, which has significant clinical characteristics and genetic typing. Clinical manifestations: the patients presented as neonatal period, infants began to appear hair loss, a few patients showed puberty onset. The eyebrow, eyelash, pubic hair, armpit hair of the patient can be affected or normal. According to the clinical characteristics of hereditary hypotrichobia can be roughly divided into the following five types: 1. Hereditary simple scalp hypodermia 2. Hereditary simple Hypoderma 3. Marie Unna type Hypoderma 4. Autosomal dominant woolly hair 5. Hair loosening syndrome and so on. With the development of molecular genetics, the pathogenetic genes of congenital hypotrichobia have been reported one after another, and our research is mainly aimed at the direct sequencing of the CDSN gene, which is the pathogenetic gene of hereditary simple scalp hypodermia. The mutation site of CDSN gene was detected. Objective to identify a new pathogenetic mutation of hereditary simple scalp hypotrichobia, and to elucidate its pathogenesis from the level of molecular genetics, and to provide theoretical basis for genetic counseling, gene diagnosis and genetic diagnosis. Rich genetic hypotrichobia genetic mutation spectrum. Materials and methods genetic investigation, laboratory examination, clinical manifestation and physical examination of a family member with hereditary simple scalp hypotrichobia were carried out. With the permission of the patient's knowledge, several cases of the disease were extracted and analyzed by scanning electron microscope. The peripheral venous blood samples were collected and the DNA samples were extracted. The primer design of previously reported CDSN gene was carried out with premier 5.0. PCR amplification technique was used to amplify exon 5 of CDSN gene of patients and other members of the family. Direct sequencing was carried out with ABI3730XL sequencer to determine the pathogenicity of mutagenesis. The sequenced data were analyzed according to whether the mutation was in accordance with the genetic rules within the family. The relationship between mutant loci and phenotypes was discussed in this paper. Results the pedigree patients showed increased scalp fat secretion, hair loss, thinning and soft, and no longer growth of 7cm at puberty. Pubic hair, armpit hair, eyebrows, eyelashes, teeth, nails and so on are not involved. Physical examination: Shenqing mind can, physical and mental development is not abnormal. The disease occurred in Schottky Field Emission High Resolution Electron Microscopy (HREM) scanning showed that the hair was normal. DNA sequencing showed that, The insertion mutation of a coding region was found in all the patients in the pedigree, and the correlation between the genotype and phenotype was not found in normal patients in all families. The insertion mutation of coding region, c. 520ins G), led to the downstream frame shift mutation, resulting in subsequent amino acid structure changes and phenotypic changes. Conclusion the CDSN gene was directly sequenced in a Chinese family with hereditary simple scalp hypotrichobia, and the result of sequencing showed that an insertion mutation c.520_521ins P.A174fsN was found.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R758.71

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