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
Microduplications are normally invisible under microscopy and were not recognized before chromosomal microarray testing was available. Although it is difficult to confirm the orientation of duplicated segments by stan...Microduplications are normally invisible under microscopy and were not recognized before chromosomal microarray testing was available. Although it is difficult to confirm the orientation of duplicated segments by standard fluorescence in situ hybridization(FISH), our data indicates that fiber-FISH analysis has the potential to reveal the orientation of duplicated and triplicated segments of chromosomes. Recurrent microduplications reciprocal to microdeletions show tandem orientations of the duplicated segments, which is consistent with a non-allelic homologous recombination mechanism. Several random duplications showed tandem configurations and inverted duplications are rare. Further analysis is required to fully elucidate the basic mechanisms underlying such duplications/triplications.展开更多
目的分析颈项透明层(nuchal translucency,NT)增厚胎儿中拷贝数变异(copy number variations,CNV)的检出率和特点,以及NT增厚与CNV的关系。方法选取2017年1月至2021年12月在内蒙古自治区妇幼保健院经孕早期超声检查NT≥2.5 mm,且后续接...目的分析颈项透明层(nuchal translucency,NT)增厚胎儿中拷贝数变异(copy number variations,CNV)的检出率和特点,以及NT增厚与CNV的关系。方法选取2017年1月至2021年12月在内蒙古自治区妇幼保健院经孕早期超声检查NT≥2.5 mm,且后续接受介入性产前诊断的334例单胎孕妇及其胎儿为研究对象,收集其产检信息、遗传学检测结果及妊娠结局。遗传学检测方法包括G显带核型分析和染色体微阵列分析(chromosomal microarray analysis,CMA)。按NT厚度、NT合并其他染色体异常高危因素分别分组分析不同临床特征下NT增厚与CNV发生率的关系。结果①共发现26例CNV,检出率为7.78%。其中,13例为致病性CNV,2例为可能致病性CNV,11例为临床意义未明的(variant of uncertain significance,VOUS)CNV。15例中13例致病性及可能致病性CNV终止妊娠,11例中9例VOUS CNV病例活产并正常发育。②不同NT厚度组间CNV的检出率,以及单纯NT增厚与NT增厚合并其他高风险因素间CNV检出率均差异无统计学意义。③26例中有9例(34.6%)为复发性微缺失微重复区域的CNV,其中5例在15q11.2区域和3例在16p12.2-13.1区域。结论CNV是NT增厚胎儿常见的遗传变异,且多数为致病性和可能致病性CNV。但NT增厚程度及是否合并其他产前筛查高危因素与CNV的发生率无明显相关性。复发性微缺失微重复区域的CNV出现频率较高值得引起关注。展开更多
目的探讨染色体核型分析联合拷贝数变异测序(copy number variation sequencing,CNV-seq)在孕中晚期产前诊断中的应用价值。方法选取2020年9月至2022年2月在首都医科大学附属北京朝阳医院产前诊断中心就诊、具备产前诊断指征且接受羊膜...目的探讨染色体核型分析联合拷贝数变异测序(copy number variation sequencing,CNV-seq)在孕中晚期产前诊断中的应用价值。方法选取2020年9月至2022年2月在首都医科大学附属北京朝阳医院产前诊断中心就诊、具备产前诊断指征且接受羊膜腔穿刺的孕妇343例,采用染色体核型分析和CNV-seq技术进行产前诊断,比较二者单独及联合应用的诊断结果。结果羊水染色体核型分析和CNV-seq同时检出了染色体数目异常14例,核型分析额外检出嵌合体1例和平衡易位3例,CNV-seq额外检出7例致病性拷贝数变异、1例可能致病性拷贝数变异和17例临床意义未明变异,CNV-seq的异常检出率(11.37%,39/343)高于染色体核型分析(5.25%,18/343),差异有显著性(P<0.05),二者联合应用的异常检出率为12.54%(43/343)。在不同产前诊断指征的孕妇中,单独及合并无创产前筛查异常者的异常检出率最高(61.54%,8/13),单独超声异常者的异常检出率为14.04%(8/57),单独高龄者的异常检出率较低(7.69%,15/195)。具有两项及以上产前诊断指征的孕妇异常检出率并不比仅有一项高危因素的孕妇高(P>0.05)。结论染色体核型分析与CNV-seq技术各具优势,二者的检测结果可以相互印证。在染色体低比例嵌合、平衡易位及倒位等方面,染色体核型分析更具优势,而CNV-seq可以检出微缺失、微重复,弥补核型分析的不足;但在临床上要依靠大量数据的积累和对最新文献的跟进,尽可能减少临床意义未明变异报告的产生。联合应用两种检测方法可降低漏诊率,有效提高产前诊断的质量。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Microduplications are normally invisible under microscopy and were not recognized before chromosomal microarray testing was available. Although it is difficult to confirm the orientation of duplicated segments by standard fluorescence in situ hybridization(FISH), our data indicates that fiber-FISH analysis has the potential to reveal the orientation of duplicated and triplicated segments of chromosomes. Recurrent microduplications reciprocal to microdeletions show tandem orientations of the duplicated segments, which is consistent with a non-allelic homologous recombination mechanism. Several random duplications showed tandem configurations and inverted duplications are rare. Further analysis is required to fully elucidate the basic mechanisms underlying such duplications/triplications.
文摘目的探讨染色体核型分析联合拷贝数变异测序(copy number variation sequencing,CNV-seq)在孕中晚期产前诊断中的应用价值。方法选取2020年9月至2022年2月在首都医科大学附属北京朝阳医院产前诊断中心就诊、具备产前诊断指征且接受羊膜腔穿刺的孕妇343例,采用染色体核型分析和CNV-seq技术进行产前诊断,比较二者单独及联合应用的诊断结果。结果羊水染色体核型分析和CNV-seq同时检出了染色体数目异常14例,核型分析额外检出嵌合体1例和平衡易位3例,CNV-seq额外检出7例致病性拷贝数变异、1例可能致病性拷贝数变异和17例临床意义未明变异,CNV-seq的异常检出率(11.37%,39/343)高于染色体核型分析(5.25%,18/343),差异有显著性(P<0.05),二者联合应用的异常检出率为12.54%(43/343)。在不同产前诊断指征的孕妇中,单独及合并无创产前筛查异常者的异常检出率最高(61.54%,8/13),单独超声异常者的异常检出率为14.04%(8/57),单独高龄者的异常检出率较低(7.69%,15/195)。具有两项及以上产前诊断指征的孕妇异常检出率并不比仅有一项高危因素的孕妇高(P>0.05)。结论染色体核型分析与CNV-seq技术各具优势,二者的检测结果可以相互印证。在染色体低比例嵌合、平衡易位及倒位等方面,染色体核型分析更具优势,而CNV-seq可以检出微缺失、微重复,弥补核型分析的不足;但在临床上要依靠大量数据的积累和对最新文献的跟进,尽可能减少临床意义未明变异报告的产生。联合应用两种检测方法可降低漏诊率,有效提高产前诊断的质量。
