[Clinical features and Y chromosome abnormalities in children with 45, X/46, XY mosaicism].

Objective: To investigate the clinical and genetic characteristics of children with 45, X/46, XY mosaicism. Methods: The retrospective study included 20 children diagnosed with 45, X/46, XY and 45, X/46, X,+mar mosaicism in the First Affiliated Hospital of Zhengzhou University from 2018 to 2022. The clinical features, gonadal pathology, treatment and follow-up were summarized. Genetic tests were performed by SRY gene test, azoospermia factor region (AZF) deletion test, copy number variation-sequencing (CNV-seq). Age at first diagnosis was compared between boys and girls using independent sample t-test. Results: The 20 patients included 3 boys and 17 girls, and the age at first diagnosis were (7.6±5.5) years, it is (2.1±1.9) years in boys, (8.7±5.4) years in girls, significantly younger for boys (t=-3.86, P=0.004). The chief complaint was external genitalia malformation for boys, and short stature (13 cases) and dysplastic external genital for girls (4 cases). Five girls presented with features of Turner syndrome. The gonadal phenotypes included mixed gonadal dysplasia (MGD, 6 cases), complete gonadal dysplasia (CGD, 10 cases), unilateral ovotestis (2 cases), possible ovaries (1 case) and undetermined gonad (1 case). One female with dysplastic genital was reassigned to male, and the gender of the remaining cases remained unchanged. Seven females were treated with recombinant human growth hormone. The height increased by (17±7) cm during the (2.9±1.2) years follow-up. No gonadal malignancy was observed. The karyotype was 45, X/46, XY in 16 cases, and 45, X/46, X,+mar in 4 cases. All of the 4 marker chromosomes were derived from Y chromosome confirmed by CNV-seq. SRY gene was detected in all 20 patients genome, and AZF deletion was found in 7 girls. Conclusions: 45, X/46, XY mosaicism presented with dysplastic external genital or female with remarkable short stature. Gonadal phenotypes included MGD, CGD and ovotestis. AZF microdeletions were found in the majority of female cases.目的： 探讨45，X/46，XY性发育异常（DSD）患儿的临床和遗传学特点。 方法： 回顾性分析2018至2022年郑州大学第一附属医院收治的20例45，X/46，XY或45，X/46，X，+mar核型的患儿，总结临床资料、性腺病理、治疗及随访，应用SRY基因检测、Y染色体无精子因子（AZF）检测、低深度全基因组拷贝数变异（CNV）测序等进行遗传学检测。采用独立样本t检验比较男童与女童组的初诊年龄差异。 结果： 20例患儿中男3例、女17例，初诊年龄（7.6±5.5）岁，男童组初诊年龄低于女童组［（2.1±1.9）比（8.7±5.4）岁，t=-3.86，P=0.004］。男童均为外生殖器发育异常，女童为身材矮小（13例）或外生殖器发育异常（4例）。5例女童伴特纳综合征表型。性腺表型为混合型性腺发育不良（MGD，6例），完全型性腺发育不良（CGD，10例），卵睾型DSD（2例），1例性腺可能为卵巢，1例暂无法确定。1例外生殖器发育异常的女童改变为男性，余性别不变。7例女童接受重组人生长激素治疗，随访时间（2.9±1.2）年，身高增长（17±7）cm。20例患儿均未见性腺恶变。16例核型为45，X/46，XY，4例核型为45，X/46，X，+mar，经CNV测序确认，额外标记染色体均为Y染色体来源。20例患儿均检测到SRY基因扩增，7例女童存在AZF缺失。 结论： 45，X/46，XY DSD患儿表现为外生殖器发育异常或女性身材矮小，性腺表型包括MGD、CGD和卵睾型等多种形式，多数女童Y染色体存在微缺失。.