Copy Number Variation Analysis of 5p Deletion Provides Accurate Prenatal Diagnosis and Reveals Candidate Pathogenic Genes.
Copy Number Variation Analysis of 5p Deletion Provides Accurate Prenatal Diagnosis and Reveals Candidate Pathogenic Genes.
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DOI：
10.3389/fmed.2022.883565
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发表时间：
2022
影响因子：
3.9
通讯作者：
He, Rong
中科院分区：
文献类型：
--
作者：
Chu, Guoming;Li, Pingping;Wen, Juan;Zheng, Gaoyan;Zhao, Yanyan;He, Rong
5p缺失综合征以猫的叫声和特殊的音色为特征，被认为是最常见的致病性拷贝数变异（CNVs）之一。5p上涉及多种基因的可变关键区域导致表型异质性，但没有特定的相关性。本研究的目的是检测5p缺失综合征的基因型-表型相关性，并重新定义5p缺失综合征的相关区域。此外，我们证明了全基因组测序（WGS）在产前诊断中鉴定染色体断点的潜在用途。招募了三个家庭，其中有接受产前诊断的妇女和两个孩子。通过核型分析、CNV-seq、荧光原位杂交、WGS和Sanger测序来鉴定染色体疾病。我们报道了三个家庭和两个孩子出现5p缺失或合并6p重复的CNVs。检测到5种不同大小的5p缺失，并确定其致病性，包括5p15.33-p15.31[1 - 770万，不确定意义家族1变异（VUS）]、5p15.33-p15.31（1-3,220,000，家族2-VUS）、5p15.33-p15.31（1-7,040,000，家族3-VUS）、5p15.33-p15.31（1-8,740,000，儿童1致病性）和5p15.31-p15.1（8,520,001-18,080,000，儿童2致病性）。在6p25.3-p24.3（1-10,420,000）处检测到一个重复，并确定可能致病。利用WGS技术成功鉴定了家族3的染色体断点。一些被认为是导致症状的关键基因被确定。重新定义了5p缺失综合征的相关区域，chr5:7,700,000-8,740,000区域被认为是猫叫声的原因。WGS在检测染色体易位方面的巨大潜力已得到证实。我们的发现可能为进一步研究相关疾病的预防、诊断和治疗铺平道路。
5p deletion syndrome, that characterized by cat-like cry and peculiar timbre of voice, is believed to be one of the most common pathogenic copy number variations (CNVs). Variable critical regions on 5p involving a variety of genes contribute to the phenotypic heterogeneity without specific correlation. The objective of this study was to examine the genotype–phenotype correlation of 5p deletion syndrome, and to redefine 5p deletion syndrome relevant regions. In addition, we demonstrate the potential use of whole genome sequencing (WGS) to identify chromosomal breakpoints in prenatal diagnosis. Three families with women undergoing prenatal diagnosis and two children were recruited. Karyotyping, CNV-seq, fluorescence in situ hybridization, WGS, and Sanger sequencing were performed to identify the chromosomal disorder. We reported three families and two children with CNVs of 5p deletion or combined 6p duplication. Five different sizes of 5p deletion were detected and their pathogenicity was determined, including 5p15.33-p15.31 [1–7,700,000, family1-variant of uncertain significance (VUS)], 5p15.33 (1–3,220,000, family 2-VUS), 5p15.33-p15.31 (1–7,040,000, family 3-VUS), 5p15.33-p15.31 (1–8,740,000, child 1-pathogenic) and 5p15.31-p15.1 (8,520,001–18,080,000, child 2-pathogenic). One duplication at 6p25.3-p24.3 (1–10,420,000) was detected and determined as likely pathogenic. The chromosomal breakpoints in family 3 were successfully identified by WGS. Some critical genes that were supposed to be causative of the symptoms were identified. Relevant region in 5p deletion syndrome was redefined, and the chr5:7,700,000–8,740,000 region was supposed to be responsible for the cat-like cry. The great potential of WGS in detecting chromosomal translocations was demonstrated. Our findings may pave the way for further research on the prevention, diagnosis, and treatment of related diseases.
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DOI：
10.1002/ajmg.c.31444
发表时间：
2015-09
期刊：
American journal of medical genetics. Part C, Seminars in medical genetics
影响因子：
--
作者：
Nguyen JM;Qualmann KJ;Okashah R;Reilly A;Alexeyev MF;Campbell DJ
通讯作者：
Campbell DJ
影响因子：
11.8
作者：
Sigg MA;Menchen T;Lee C;Johnson J;Jungnickel MK;Choksi SP;Garcia G 3rd;Busengdal H;Dougherty GW;Pennekamp P;Werner C;Rentzsch F;Florman HM;Krogan N;Wallingford JB;Omran H;Reiter JF
通讯作者：
Reiter JF
影响因子：
2
作者：
Shi, Panlai;Li, Rui;Kong, Xiangdong
通讯作者：
Kong, Xiangdong
12例产前惊呼综合征的临床和分子特征
影响因子：
2
作者：
Peng, Ying;Pang, Jialun;Wang, Hua
通讯作者：
Wang, Hua
DOI：
10.1002/ajmg.10261
发表时间：
2002-03-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Levy, B;Dunn, TM;Kardon, NB
通讯作者：
Kardon, NB