Genetic and Clinical Characteristics of 185 Japanese Children With 46,XY Differences of Sex Development

被引:1
作者
Hayashi, Mie [1 ]
Narumi, Satoshi [1 ,2 ]
Sato, Takeshi [1 ]
Amano, Naoko [1 ]
Suwanai, Ayuko Suzuki [1 ]
Haruna, Hidenori [3 ]
Muroya, Koji [4 ]
Adachi, Masanori [4 ]
Asanuma, Hiroshi [5 ]
Ohashi, Hirofumi [6 ]
Ishii, Tomohiro [1 ]
Hasegawa, Tomonobu [1 ]
机构
[1] Keio Univ, Dept Pediat, Sch Med, 35 Shinanomachi,Shinjuku Ku, Tokyo 1608582, Japan
[2] Natl Res Inst Child Hlth & Dev, Dept Mol Endocrinol, Tokyo 1578535, Japan
[3] Juntendo Univ, Dept Pediat & Adolescent Med, Sch Med, Tokyo 1138421, Japan
[4] Kanagawa Childrens Med Ctr, Dept Endocrinol & Metab, Yokohama 2328555, Japan
[5] Keio Univ, Dept Urol, Sch Med, Tokyo 1608582, Japan
[6] Saitama Childrens Med Ctr, Div Med Genet, Saitama 3308777, Japan
关键词
differences of sex development; 46; XY; genetic disorder; ambiguous genitalia; M & uuml; llerian derivatives; DISORDERS; MANAGEMENT; MUTATIONS; PHENOTYPE; DIAGNOSIS; VARIANTS; GENOTYPE; DEFECTS; NR5A1; DSD;
D O I
10.1210/clinem/dgae813
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: 46,XY differences of sex development (DSD) are heterogeneous in etiology. The detailed phenotypes of 46,XY DSD patients with monogenic disorders have not been fully elucidated. Objectives: To estimate the proportion of monogenic disorders in 46,XY DSD and to characterize the clinical phenotypes of patients with monogenic disorders. Methods: A total of 185 Japanese patients (178 families) were enrolled. We sequenced 25 genes related to 46,XY DSD, and assessed the pathogenicity of the identified sequence variants according to the American College of Medical Genetics and Genomics guidelines, supplemented by in silico or in vitro analyses. We analyzed the clinical phenotypes of patients with monogenic disorders, with particular attention to the external or internal genitalia. Results: We identified 51 patients (47 families) with any monogenic disorders (26%), who possessed pathogenic variants in AR (11%), SRD5A2 (4.5%), NR5A1 (4.0%), SRY (2.8%), WT1 (1.1%), STAR (1.1%), CYP17A1 (0.56%), HSD3B2 (0.56%), or MAP3K1 (0.56%). The proportion of monogenic disorders was significantly higher in subjects with detected M & uuml;llerian derivatives (57%) than in those undetected (26%) (P = 0.029), in subjects with female-typical genitalia (91%) than those with ambiguous genitalia (19%) (P < 0.001). Conclusions: The proportion of monogenic disorders in Japanese 46,XY DSD patients was approximately 26%. Monogenic disorders were frequent among patients with severe undermasculinization of the external or internal genitalia.
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页数:9
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