■5p删除综合征,其特征是像猫一样的哭泣和独特的声音,被认为是最常见的致病拷贝数变异(CNV)之一。5p上涉及多种基因的可变关键区有助于表型异质性,而没有特定的相关性。这项研究的目的是检查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.
■招募了三个接受产前诊断的妇女家庭和两个孩子。核型分析,CNV-seq,荧光原位杂交,WGS,进行Sanger测序以鉴定染色体疾病。
■我们报道了3个家庭和2个有5p缺失或合并6p重复的CNVs的儿童。检测到5个不同大小的5p缺失,并确定其致病性,包括5p15.33-p15.31[1-7,700,000,具有不确定意义的家族变体(VUS)],5p15.33(1-3,220,000,家庭2-VUS),5p15.33-p15.31(1-7,040,000,家庭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,并确定为可能致病。WGS成功鉴定了家族3中的染色体断点。
■确定了一些可能导致症状的关键基因。重新定义了5p缺失综合征的相关区域,而chr5:7,700,000-8,74万地区应该是猫般的哭声的原因。证明了WGS在检测染色体易位方面的巨大潜力。我们的发现可能为进一步的预防研究铺平道路,诊断,以及相关疾病的治疗。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.