先天性眼球震颤家系与先天性肾病综合征家系的遗传学分析
发布时间：2019-01-01 16:01
【摘要】：第一部分先天性眼球震颤家系的遗传学分析 背景：先天性眼球震颤(Congenital nystagmus, CN)是一种较为常见的眼球异常运动性疾病。以双眼或单眼不自主的、有节律的眼球往返运动为典型症状,多在出生时及出生后几个月内起病。眼球震颤主要可分为水平型、垂直型与旋转型三种,以水平型最为常见。CN具有遗传异质性,目前为止,已报道的与CN相关致病基因有两个：FRMD7和GPR143。 目的：对一先天性眼球震颤家系进行遗传学分析,并对高危胎儿进行产前诊断。 方法：对家系部分成员进行临床眼科检查；应用聚合酶链反应(PCR)和DNA测序的方法,对先证者的FRMD7和GPR143进行突变检测；对测序发现的性质未知的碱基改变在相关家系成员及正常人群中进行进一步检查。 结果：患者存在先天性眼球震颤、眼底色素减退、黄斑发育不良等表型；检测到该家系中患者与胎儿GPR143存在c.658+1 gt剪接突变,其他家系成员与50例正常对照未发现此突变。FRMD7未发现突变。 结论：剪接突变c.658+1 gt是GPR143的新发致病突变。 第二部分先天性肾病综合征家系的遗传学分析 背景：患有先天性肾病综合征(Congenital nephrotic syndrome,CNS)的婴儿约40%由NPHS1突变引起。由NPHS1突变导致芬兰型先天性肾病综合征(Finnish congenital nephrotic,CNF),是一种常见的CNS.CNF发病早,多于3个月内发病,病程重,主要表现为蛋白尿等。在芬兰,其发病率为1/8200新生活婴,其它国家发病率较低,国内尚无此病发病率的报道。CNF目前除肾移植外尚无有效治疗方法,因此有必要进行基因诊断和产前诊断以预防患儿的出生。 目的：对曾生育2例先天性肾病综合征患儿的夫妇进行相关基因突变分析,并对高危胎儿进行产前诊断。 方法：应用聚合酶链反应(PCR)和DNA测序的方法,对该夫妇的NPHS1和NPHS2进行突变检测；对测序发现的性质未知的碱基改变在胎儿及正常人群中进行进一步检查。 结果：检测到孕妇NPHS1基因在17号外显子上存在1个未见报道的错义突变c.2225CT;丈夫NPHS1基因在20号外显子也存在-个未见报道的无义突变c.2783CA;胎儿与50例家系外正常人均未发现这两个突变。NPHS2基因未发现致病突变。 结论：错义突变c.2225CT和无义突变c.2783CA是NPHS1基因的两个新发致病突变；胎儿未遗传这两个突变位点,出生后不会患与这两个突变相关的先天性肾病综合征。
[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.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R777.46;R692.3
本文编号：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.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R777.46;R692.3
【参考文献】
相关期刊论文 前3条
1 范青锋;丁洁;;肾病综合征分子遗传学研究进展[J];临床儿科杂志;2007年04期
2 余自华,丁洁,管娜,石岩,张敬京,黄建萍,姚勇,杨霁云;一个中国汉族人家族性激素耐药型肾病综合征家系NPHS2基因新突变[J];中华儿科杂志;2004年02期
3 石岩,丁洁,刘景城,王华,卜定方;中国人先天性肾病综合征NPHS1基因突变[J];中华儿科杂志;2005年11期
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