目的:探讨一例罕见性发育障碍病例的遗传基础。
方法:收集患者的临床资料。染色体核型分析,SRY基因检测,全外显子组测序(WES),低覆盖率大规模平行拷贝数变异测序(CNV-seq),荧光原位杂交(FISH),进行全基因组测序(WGS)。
结果:患者,一个14岁的女性,表现为身材矮小和第二性特征的发育不良。发现她具有46,XY核型,并且SRY基因呈阳性。WES没有发现致病变异,除了在Yp11.32q12的重复。结果CNV-seq为47,XYY。FISH已经证实了双中心Y染色体的镶嵌性。WGS发现Yp11.32q11.223上有23.66Mb重复,Yq11.223q11.23上有5.16Mb缺失。断点被映射在chrY:23656267。患者的核型最终被确定为46,X,psuidic(Y)(q11.223)/46,X,德尔(Y)(q11.223)。
结论:多种方法的结合促进了该患者遗传病因的澄清,为临床诊断和治疗提供参考。
OBJECTIVE: To explore the genetic basis for a rare
case with Disorder of sex development.
METHODS: Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out.
RESULTS: The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient\'s karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223).
CONCLUSIONS: The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.