先天性眼球震顫家系與先天性腎病綜合征家系的遺傳學(xué)分析
發(fā)布時間：2019-01-01 16:01
【摘要】：第一部分先天性眼球震顫家系的遺傳學(xué)分析 背景：先天性眼球震顫(Congenital nystagmus, CN)是一種較為常見的眼球異常運(yùn)動性疾病。以雙眼或單眼不自主的、有節(jié)律的眼球往返運(yùn)動為典型癥狀,多在出生時及出生后幾個月內(nèi)起病。眼球震顫主要可分為水平型、垂直型與旋轉(zhuǎn)型三種,以水平型最為常見。CN具有遺傳異質(zhì)性,目前為止,已報道的與CN相關(guān)致病基因有兩個：FRMD7和GPR143。 目的：對一先天性眼球震顫家系進(jìn)行遺傳學(xué)分析,并對高危胎兒進(jìn)行產(chǎn)前診斷。 方法：對家系部分成員進(jìn)行臨床眼科檢查；應(yīng)用聚合酶鏈反應(yīng)(PCR)和DNA測序的方法,對先證者的FRMD7和GPR143進(jìn)行突變檢測；對測序發(fā)現(xiàn)的性質(zhì)未知的堿基改變在相關(guān)家系成員及正常人群中進(jìn)行進(jìn)一步檢查。 結(jié)果：患者存在先天性眼球震顫、眼底色素減退、黃斑發(fā)育不良等表型；檢測到該家系中患者與胎兒GPR143存在c.658+1 gt剪接突變,其他家系成員與50例正常對照未發(fā)現(xiàn)此突變。FRMD7未發(fā)現(xiàn)突變。 結(jié)論：剪接突變c.658+1 gt是GPR143的新發(fā)致病突變。 第二部分先天性腎病綜合征家系的遺傳學(xué)分析 背景：患有先天性腎病綜合征(Congenital nephrotic syndrome,CNS)的嬰兒約40%由NPHS1突變引起。由NPHS1突變導(dǎo)致芬蘭型先天性腎病綜合征(Finnish congenital nephrotic,CNF),是一種常見的CNS.CNF發(fā)病早,多于3個月內(nèi)發(fā)病,病程重,主要表現(xiàn)為蛋白尿等。在芬蘭,其發(fā)病率為1/8200新生活嬰,其它國家發(fā)病率較低,國內(nèi)尚無此病發(fā)病率的報道。CNF目前除腎移植外尚無有效治療方法,因此有必要進(jìn)行基因診斷和產(chǎn)前診斷以預(yù)防患兒的出生。 目的：對曾生育2例先天性腎病綜合征患兒的夫婦進(jìn)行相關(guān)基因突變分析,并對高危胎兒進(jìn)行產(chǎn)前診斷。 方法：應(yīng)用聚合酶鏈反應(yīng)(PCR)和DNA測序的方法,對該夫婦的NPHS1和NPHS2進(jìn)行突變檢測；對測序發(fā)現(xiàn)的性質(zhì)未知的堿基改變在胎兒及正常人群中進(jìn)行進(jìn)一步檢查。 結(jié)果：檢測到孕婦NPHS1基因在17號外顯子上存在1個未見報道的錯義突變c.2225CT;丈夫NPHS1基因在20號外顯子也存在-個未見報道的無義突變c.2783CA;胎兒與50例家系外正常人均未發(fā)現(xiàn)這兩個突變。NPHS2基因未發(fā)現(xiàn)致病突變。 結(jié)論：錯義突變c.2225CT和無義突變c.2783CA是NPHS1基因的兩個新發(fā)致病突變；胎兒未遺傳這兩個突變位點(diǎn),出生后不會患與這兩個突變相關(guān)的先天性腎病綜合征。
[Abstract]:Part I genetic analysis of congenital nystagmus background: congenital nystagmus (Congenital nystagmus, CN) is a common abnormal ocular movement disease. It is characterized by involuntary rhythmic movement of the eyes, usually occurring at birth and within a few months after birth. Nystagmus can be divided into horizontal type, vertical type and rotation type, and horizontal type is the most common type. CN has genetic heterogeneity, so far, there are two reported pathogenicity genes associated with CN: FRMD7 and GPR143.. Objective: to analyze the genetics of a pedigree with congenital nystagmus and to make prenatal diagnosis of high-risk fetus. Methods: clinical ophthalmological examination was performed on some family members and mutation of FRMD7 and GPR143 in proband was detected by polymerase chain reaction (PCR) and DNA sequencing. The unknown nucleotide changes found by sequencing were further examined in the relevant family members and the normal population. Results: the patients had congenital nystagmus, hypochromatic fundus, macular dysplasia and other phenotypes. It was found that there was a c.6581 gt splicing mutation in GPR143 of patient and fetus in this family, but no mutation was found in other family members and 50 normal controls. No mutation was found in FRMD7. Conclusion: splicing mutation c. 658 1 gt is a new pathogenic mutation of GPR143. Background: about 40% of infants with congenital nephrotic syndrome (Congenital nephrotic syndrome,CNS) are caused by NPHS1 mutation. Finnish congenital nephrotic syndrome (Finnish congenital nephrotic,CNF) caused by NPHS1 mutation is a common CNS.CNF with early onset, more than 3 months of onset and severe course of disease, mainly characterized by proteinuria. In Finland, the incidence rate is 1 / 8200 newborns, while in other countries the incidence is relatively low. There are no reports of this disease in the country. There is no effective treatment for CNF except for kidney transplantation. Therefore, it is necessary to carry out genetic and prenatal diagnosis to prevent the birth of children. Objective: to analyze the gene mutation of 2 children with congenital nephrotic syndrome and to make prenatal diagnosis of high-risk fetuses. Methods: polymerase chain reaction (PCR) and DNA sequencing were used to detect the mutation of NPHS1 and NPHS2 in the couple. Results: an unreported missense mutation c.2225CTin the NPHS1 gene of pregnant women was detected in exon 17, and a missense mutation c.2783CAat in the husband NPHS1 gene was found in exon 20. The two mutations were not found in the fetus and 50 normal individuals outside the family. No pathogenic mutations were found in the NPHS2 gene. Conclusion: missense mutation c.2225CT and nonsense mutation c.2783CA are two new pathogenetic mutations of NPHS1 gene and the fetal uninherited two mutation sites will not have congenital nephrotic syndrome associated with these two mutations after birth.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R777.46;R692.3
本文編號：2397782
[Abstract]:Part I genetic analysis of congenital nystagmus background: congenital nystagmus (Congenital nystagmus, CN) is a common abnormal ocular movement disease. It is characterized by involuntary rhythmic movement of the eyes, usually occurring at birth and within a few months after birth. Nystagmus can be divided into horizontal type, vertical type and rotation type, and horizontal type is the most common type. CN has genetic heterogeneity, so far, there are two reported pathogenicity genes associated with CN: FRMD7 and GPR143.. Objective: to analyze the genetics of a pedigree with congenital nystagmus and to make prenatal diagnosis of high-risk fetus. Methods: clinical ophthalmological examination was performed on some family members and mutation of FRMD7 and GPR143 in proband was detected by polymerase chain reaction (PCR) and DNA sequencing. The unknown nucleotide changes found by sequencing were further examined in the relevant family members and the normal population. Results: the patients had congenital nystagmus, hypochromatic fundus, macular dysplasia and other phenotypes. It was found that there was a c.6581 gt splicing mutation in GPR143 of patient and fetus in this family, but no mutation was found in other family members and 50 normal controls. No mutation was found in FRMD7. Conclusion: splicing mutation c. 658 1 gt is a new pathogenic mutation of GPR143. Background: about 40% of infants with congenital nephrotic syndrome (Congenital nephrotic syndrome,CNS) are caused by NPHS1 mutation. Finnish congenital nephrotic syndrome (Finnish congenital nephrotic,CNF) caused by NPHS1 mutation is a common CNS.CNF with early onset, more than 3 months of onset and severe course of disease, mainly characterized by proteinuria. In Finland, the incidence rate is 1 / 8200 newborns, while in other countries the incidence is relatively low. There are no reports of this disease in the country. There is no effective treatment for CNF except for kidney transplantation. Therefore, it is necessary to carry out genetic and prenatal diagnosis to prevent the birth of children. Objective: to analyze the gene mutation of 2 children with congenital nephrotic syndrome and to make prenatal diagnosis of high-risk fetuses. Methods: polymerase chain reaction (PCR) and DNA sequencing were used to detect the mutation of NPHS1 and NPHS2 in the couple. Results: an unreported missense mutation c.2225CTin the NPHS1 gene of pregnant women was detected in exon 17, and a missense mutation c.2783CAat in the husband NPHS1 gene was found in exon 20. The two mutations were not found in the fetus and 50 normal individuals outside the family. No pathogenic mutations were found in the NPHS2 gene. Conclusion: missense mutation c.2225CT and nonsense mutation c.2783CA are two new pathogenetic mutations of NPHS1 gene and the fetal uninherited two mutation sites will not have congenital nephrotic syndrome associated with these two mutations after birth.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R777.46;R692.3
【參考文獻(xiàn)】
相關(guān)期刊論文 前3條
1 范青鋒;丁潔;;腎病綜合征分子遺傳學(xué)研究進(jìn)展[J];臨床兒科雜志;2007年04期
2 余自華,丁潔,管娜,石巖,張敬京,黃建萍,姚勇,楊霽云;一個中國漢族人家族性激素耐藥型腎病綜合征家系NPHS2基因新突變[J];中華兒科雜志;2004年02期
3 石巖,丁潔,劉景城,王華,卜定方;中國人先天性腎病綜合征NPHS1基因突變[J];中華兒科雜志;2005年11期
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