400例性发育异常患者遗传学病因检测与特征分析

Genetic etiology testing and characteristic analysis of 400 patients with disorder sexual development

目的应用多种遗传学技术检测诊断400例性发育异常(DSD)患者的遗传学病因,并总结分析其临床特征。方法选取2018年1月至2023年3月该院收治的400例确诊为DSD的患者作为研究对象,运用G-显带染色体核型分析、荧光原位杂交(FISH)、多重链接探针扩增技术(MLPA)、高通量测序的低深度全基因组测序(CNV-seq)、全外显子组测序技术(WES)、全基因组测序(WGS)等技术进行检测和定位,查找患者遗传学病因。结果经G-显带染色体核型分析,以及FISH、MLPA对核型分析结果进行验证,明确诊断45,X特纳综合征及其变异型136例(34.00%),47,XXY克氏综合征及其变异型187例(46.75%);经G-显带染色体核型分析、CNV-seq、WES、WGS、一代测序技术诊断46,XX DSD 17例(4.25%)、46,XY DSD 35例(8.75%);经G-显带染色体核型分析和FISH、MLPA验证诊断性染色体核型异常DSD 25例(6.25%)。结论联合应用G-显带染色体核型、FISH、CNV-seq、WES等多种遗传学方法,能准确发现DSD的遗传学病因,建立基因型与表现型之间的良好关系。

Objective To detect and diagnose the genetic etiology of 400 patients with disorder of sex development(DSD)by various genetic techniques,and summarize and analyze their clinical characteristics.Methods Four hundred patients diagnosed with DSD in the hospital from January 2018 to March 2023 were selected as research objects,and G-banding chromosome karyotype analysis,fluorescence in situ hybridization(FISH),multiplex ligation-dependent probe amplification(MLPA),copy number variation sequencing(CNV-seq)with high-throughput sequencing,whole exome sequencing(WES),whole genome sequencing(WGS)and other techniques were adopted to detect and locate the genetic causes of the patients.Results After G-banding chromosomal karyotype analysis and verification of the results by FISH and MLPA,136 cases(34.00%)of 45,X Turner syndrome and its variants were diagnosed definitely,as well as 187 cases(46.75%)of 47,XXY Klinefelter syndrome and its variants.After G-banding chromosomal karyotype analysis,CNV-seq,WES,WGS and first-generation sequencing technology,17 cases(4.25%)of 46,XX DSD and 35 cases(8.75%)of 46,XY DSD were diagnosed.After G-banding chromosomal karyotype analysis and verification by FISH and MLPA,25 cases(6.25%)of diagnostic chromosomal karyotype abnormalities were diagnosed.Conclusion Combination of multiple genetic methods such as G-banded chromosome karyotype,FISH,CNV-seq and WES is possible to accurately identify the genetic causes of DSD and establish a good relationship between genotype and phenotype.