BACKGROUND Copy number variation(CNV)has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research.1q21.1 microduplication syndrome is a rare ...BACKGROUND Copy number variation(CNV)has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research.1q21.1 microduplication syndrome is a rare CNV disease that can manifest as multiple congenital developmental disorders,autism spectrum disorders,congenital malformations,and congenital heart defects with genetic heterogeneity.CASE SUMMARY We reported a pediatric patient with 1q21.1 microduplication syndrome,and carried out a literature review to determine the correlation between 1q21.1microduplication and its phenotypes.We summarized the patient’s medical history and clinical symptoms,and extracted genomic DNA from the patient,her parents,elder brother,and sister.The patient was an 8-mo-old girl who was hospitalized for recurrent convulsions over a 2-mo period.Whole exon sequencing and whole genome low-depth sequencing(CNV-seq)were then performed.Whole exon sequencing detected a 1.58-Mb duplication in the CHR1:145883867-147465312 region,which was located in the 1q21.1 region.Family analysis showed that the pathogenetic duplication fragment,which was also detected in her elder brother’s DNA originated from the mother.CONCLUSION Whole exon sequencing combined with quantitative polymerase chain reaction can provide an accurate molecular diagnosis in children with 1q21.1 microduplication syndrome,which is of great significance for genetic counseling and early intervention.展开更多
目的应用微阵列比较基因组杂交技术探讨胎儿先天性泌尿系统畸形的遗传学病因。方法选取32例经产前超声检查提示发生不同程度泌尿系统畸形并且常规G显带核型分析方法未发现异常的胎儿病例及其父母的DNA，按照标准的Affymetri xcytogenet...目的应用微阵列比较基因组杂交技术探讨胎儿先天性泌尿系统畸形的遗传学病因。方法选取32例经产前超声检查提示发生不同程度泌尿系统畸形并且常规G显带核型分析方法未发现异常的胎儿病例及其父母的DNA，按照标准的Affymetri xcytogenetic2．7M芯片的操作手册进行杂交、洗涤及全基因组扫描，应用配套的CHAS软件分析结果。结果微阵列比较基因组杂交技术检测发现9例胎儿基因组发生了不平衡的拷贝数变异（copy number variations，CNVs），检出率为28％。其中4例CNVs遗传自亲代（12．5％）；2例CNVs在相关数据库中提示在正常人基因组中存在（6％）；3例是新发的致病性CNVs（9％），并且这3例胎儿样本均发生了染色体1q21．1微缺失和微重复，异常片段内包含与泌尿生殖系统功能密切相关的PDZK1基因。结论先天性泌尿系统畸形胎儿基因组发生不平衡畸变的几率约为28％，其中致病性的基因组不平衡异常约占9％。染色体lq21．1区带DNA拷贝数改变是导致先天性泌尿系统畸形的病因之一，其致病机制可能与PDZK1基因的异常表达有关。展开更多
文摘BACKGROUND Copy number variation(CNV)has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research.1q21.1 microduplication syndrome is a rare CNV disease that can manifest as multiple congenital developmental disorders,autism spectrum disorders,congenital malformations,and congenital heart defects with genetic heterogeneity.CASE SUMMARY We reported a pediatric patient with 1q21.1 microduplication syndrome,and carried out a literature review to determine the correlation between 1q21.1microduplication and its phenotypes.We summarized the patient’s medical history and clinical symptoms,and extracted genomic DNA from the patient,her parents,elder brother,and sister.The patient was an 8-mo-old girl who was hospitalized for recurrent convulsions over a 2-mo period.Whole exon sequencing and whole genome low-depth sequencing(CNV-seq)were then performed.Whole exon sequencing detected a 1.58-Mb duplication in the CHR1:145883867-147465312 region,which was located in the 1q21.1 region.Family analysis showed that the pathogenetic duplication fragment,which was also detected in her elder brother’s DNA originated from the mother.CONCLUSION Whole exon sequencing combined with quantitative polymerase chain reaction can provide an accurate molecular diagnosis in children with 1q21.1 microduplication syndrome,which is of great significance for genetic counseling and early intervention.
文摘目的应用微阵列比较基因组杂交技术探讨胎儿先天性泌尿系统畸形的遗传学病因。方法选取32例经产前超声检查提示发生不同程度泌尿系统畸形并且常规G显带核型分析方法未发现异常的胎儿病例及其父母的DNA，按照标准的Affymetri xcytogenetic2．7M芯片的操作手册进行杂交、洗涤及全基因组扫描，应用配套的CHAS软件分析结果。结果微阵列比较基因组杂交技术检测发现9例胎儿基因组发生了不平衡的拷贝数变异（copy number variations，CNVs），检出率为28％。其中4例CNVs遗传自亲代（12．5％）；2例CNVs在相关数据库中提示在正常人基因组中存在（6％）；3例是新发的致病性CNVs（9％），并且这3例胎儿样本均发生了染色体1q21．1微缺失和微重复，异常片段内包含与泌尿生殖系统功能密切相关的PDZK1基因。结论先天性泌尿系统畸形胎儿基因组发生不平衡畸变的几率约为28％，其中致病性的基因组不平衡异常约占9％。染色体lq21．1区带DNA拷贝数改变是导致先天性泌尿系统畸形的病因之一，其致病机制可能与PDZK1基因的异常表达有关。
