Mi Manli, Xia Junke, Hou Yaqin, Dai Peng, Wang Yanan, Kong Xiangdong
Department of Medical Genetics and Prenatal Diagnosis, Luoyang Maternal and Child Health Care Hospital, Luoyang, Henan 471000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Nov 10;40(11):1430-1435. doi: 10.3760/cma.j.cn511374-20210715-00598.
To explore the genetic basis for a rare case with Disorder of sex development.
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.
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).
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.
探究一例性发育障碍罕见病例的遗传基础。
收集该患者的临床资料。进行了染色体核型分析、SRY基因检测、全外显子组测序（WES）、低覆盖度大规模平行拷贝数变异测序（CNV-seq）、荧光原位杂交（FISH）及全基因组测序（WGS）。
该患者为14岁女性，表现为身材矮小及第二性征发育异常。其染色体核型为46,XY，SRY基因检测呈阳性。WES未发现致病变异，仅在Yp11.32q12处有一个重复。CNV-seq结果为47,XYY。FISH证实存在双着丝粒Y染色体的嵌合体。WGS发现Yp11.32q11.223处有23.66 Mb的重复以及Yq11.223q11.23处有5.16 Mb的缺失。断点定位于chrY: 236,562,67。该患者的核型最终确定为46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223)。
多种方法的联合应用有助于明确该患者的遗传病因，为临床诊断和治疗提供了参考。
