Medical Genetics Institute of Henan Province, Henan Provincial Peoples Hospital, Zhengzhou, 450003, Henan, China.
Department of Medical Laboratory of Central China Fuwai Hospital, Zhengzhou, 450003, Henan, China.
Appl Biochem Biotechnol. 2023 Oct;195(10):5792-5801. doi: 10.1007/s12010-023-04377-1. Epub 2023 Jan 28.
This study is to identify the pathogenic mutation of a child with Sots syndrome and provide prenatal diagnosis for his pregnant mother. Chromosome microarray technology was used to detect whether there were minor deletions/duplication in patients' chromosomes. The gene mutation of patients was screened by next-generation sequencing technology, and it was verified by Sanger sequencing. Prenatal diagnosis of the fetus was conducted according to the selected pathogenic sites, and genetic counseling was conducted for her parents. Chromosome microarray results showed that there was no minor deletion in a chromosome 5q35 region, and the second-generation sequencing results showed that there was a c.4138delG heterozygous mutation in the patient's NSD1 gene, and the pathogenic of this mutation was not reported in related databases. Sanger sequencing found that there was a c.4138delG heterozygous mutation in the NSD1 gene of the patient and her parents' genotype at this locus was wild type. The prenatal gene test results indicated that there was heterozygous mutation of NSD1 gene c.4138delG in the fetus, so it was suggested to terminate the pregnancy. Gentling results indicated that the fetus and the patient inherited the same maternal chromosome 5. The heterozygous mutation of NSD1 gene c.4138delG is the pathogenic mutation of this Sots syndrome patient, and the mother may be germinal mosaicism.
本研究旨在鉴定一名 Sotos 综合征患儿的致病突变，并为其孕妇提供产前诊断。采用染色体微阵列技术检测患者染色体是否存在微小缺失/重复。通过下一代测序技术筛选患者的基因突变，并通过 Sanger 测序进行验证。根据选定的致病位点对胎儿进行产前诊断，并对其父母进行遗传咨询。染色体微阵列结果显示，染色体 5q35 区域无微小缺失，二代测序结果显示患者 NSD1 基因存在 c.4138delG 杂合突变，该突变的致病性在相关数据库中未报道。Sanger 测序发现患者及其父母在该位点的基因型均为杂合突变 c.4138delG。产前基因检测结果提示胎儿 NSD1 基因 c.4138delG 存在杂合突变，建议终止妊娠。遗传结果表明胎儿与患者从母亲处继承了相同的染色体 5。NSD1 基因 c.4138delG 的杂合突变是该 Sotos 综合征患者的致病突变，母亲可能为生殖细胞嵌合体。
