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.

5p 缺失综合征，以猫样哭声和特殊音色为特征，被认为是最常见的致病性拷贝数变异 (CNV) 之一。5p 上涉及多种基因的可变关键区域有助于表型异质性，但没有特定的相关性。本研究的目的是检验 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，我们展示了全基因组测序（WGS）在产前诊断中识别染色体断点的潜在用途。

招募了三个有接受产前诊断的妇女和两个孩子的家庭。核型分析、CNV-seq、荧光原位进行杂交、WGS 和 Sanger 测序以确定染色体疾病。

我们报告了三个家庭和两个孩子的 CNVs 5p 缺失或组合 6p 重复。检测到五种不同大小的 5p 缺失并确定其致病性，包括 5p15.33-p15.31 [1–7,700,000, family1-variant of undefined显着性(VUS)]、5p15.33 (1–3,220,000, family 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）。检测到 6p25.3-p24.3 (1–10,420,000) 处的一个重复并确定为可能致病。WGS成功鉴定了家族3的染色体断点。

确定了一些被认为是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，chr5:7,700,000-8,740,000 区域被认为是造成猫样哭声的原因。WGS 在检测染色体易位方面的巨大潜力得到了证实。我们的研究结果可能为进一步研究相关疾病的预防、诊断和治疗铺平道路。