Genetic analysis of a rare case with Disorder of sex development due to structural rearrangement of Y chromosome
米蔓丽 1夏俊珂 2侯雅勤 2代鹏 2王亚男 1孔祥东 2许芯
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作者信息
1. 1洛阳市妇幼保健院遗传与产前诊断科，洛阳 471000
2. 2郑州大学第一附属医院遗传与产前诊断中心，郑州 450052
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摘要
目的 探讨1例罕见的Y染色体重排致性发育异常(DSD)患者的遗传学病因。 方法 选取2018年5月2日因"身材矮小，第二性征发育不良"就诊于郑州大学第一附属医院的1例性发育异常女性患儿作为研究对象，收集患儿的临床资料。联合应用染色体G显带核型分析、SRY基因检测、全外显子测序(WES)、低深度全基因组测序拷贝数变异分析技术(CNV-seq)、荧光原位杂交技术(FISH)、全基因组测序(WGS)对患者进行遗传学检测。患儿遗传学特征明确后，给予相应治疗。 结果 患儿年龄为14岁，社会性别为女性，身材矮小，毛发旺盛，皮肤粗糙。外周血染色体核型为46，XY，且携带SRY基因。WES未检测到相关基因的致病性变异，但发现Yp11.32q12处存在59.37Mb重复。CNV-seq结果为47，XYY，外周血FISH结果提示患者为双着丝粒Y染色体嵌合体携带者，WGS发现Yp11.32q11.223存在大小为23.66 Mb的重复，同时Yq11.223q11.23存在约5.16 Mb的缺失，断裂点位于chrY：23656267。综合分析，患者的染色体核型应为46，X，psu idic(Y)(q11.223)[87]/46，X，del(Y)(q11.223)[13]。手术探查结果示性腺器官为卵巢组织，激素替代治疗后患儿有月经来潮，第二性征发育良好。 结论 联合多种遗传学检测明确了患儿的遗传学病因，为患儿的诊断及治疗提供了帮助。 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). Conclusion 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.
Abstract
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). Conclusion 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.
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