Abstract：
OBJECTIVE: The clinical and molecular genetic characteristics of 46,XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease.
METHODS: The clinical data of children with NR5A1 gene variants diagnosed at the Children\'s Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics.
RESULTS: At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1 ~ 9), including micropenis (100.0%), hypospadias (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~ Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomal karyotypes were 46,XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022.
CONCLUSIONS: The clinical phenotype of 46,XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.
METHODS: The clinical data of children with NR5A1 gene variants diagnosed at the Children\'s Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics.
RESULTS: At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1 ~ 9), including micropenis (100.0%), hypospadias (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~ Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomal karyotypes were 46,XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022.
CONCLUSIONS: The clinical phenotype of 46,XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.
摘要：
目的：分析15例NR5A1基因变异导致的46,XY性发育障碍的临床和分子遗传学特征，以提高对本病的认识。
方法：回顾性分析2016年3月至2021年12月在郑州大学附属儿童医院确诊的NR5A1基因变异患儿的临床资料。进行全外显子组测序以确认候选位点，进行Sanger测序进行验证。根据患者的疾病特点进行治疗和随访。
结果：在最初诊断时，15例中有5例为女性，10例为男性。性腺组织为睾丸，无残留的苗勒管或关节结构，并且都有不同程度的生殖器异常。EMS男性气质平均得分为4.8分(1~9分),包括微阴茎（100.0%），尿道下裂(86.7%),阴囊未融合(46.7%),睾丸位置异常（60.0%），其中尿道下裂为Ⅱ°~Ⅳ°。5例生长迟缓患者无皮肤色素沉着。染色体核型为46，XY，促肾上腺皮质激素和皮质醇水平正常，电解质水平正常，HCG刺激试验5例反应正常,9例低反应。抗苗勒管激素和他汀类药物B随年龄异常下降。在15名儿童中共检测到14种NR5A1变异，其中大部分发生在外显子4,截至2022年12月,其中9个变异位点未纳入HGMD数据库.
结论：由NR5A1基因变异引起的46,XY异常性发育的临床表型广泛，外生殖器表现出不同程度的男性化不足。肾上腺受累是罕见的。
方法：回顾性分析2016年3月至2021年12月在郑州大学附属儿童医院确诊的NR5A1基因变异患儿的临床资料。进行全外显子组测序以确认候选位点，进行Sanger测序进行验证。根据患者的疾病特点进行治疗和随访。
结果：在最初诊断时，15例中有5例为女性，10例为男性。性腺组织为睾丸，无残留的苗勒管或关节结构，并且都有不同程度的生殖器异常。EMS男性气质平均得分为4.8分(1~9分),包括微阴茎（100.0%），尿道下裂(86.7%),阴囊未融合(46.7%),睾丸位置异常（60.0%），其中尿道下裂为Ⅱ°~Ⅳ°。5例生长迟缓患者无皮肤色素沉着。染色体核型为46，XY，促肾上腺皮质激素和皮质醇水平正常，电解质水平正常，HCG刺激试验5例反应正常,9例低反应。抗苗勒管激素和他汀类药物B随年龄异常下降。在15名儿童中共检测到14种NR5A1变异，其中大部分发生在外显子4,截至2022年12月,其中9个变异位点未纳入HGMD数据库.
结论：由NR5A1基因变异引起的46,XY异常性发育的临床表型广泛，外生殖器表现出不同程度的男性化不足。肾上腺受累是罕见的。
