María Guadalupe Ortiz-López, Katy Sánchez-Pozos, Charmina Aguirre-Alvarado, Vihko Pirkko, Marta Menjivar
Laboratorio de Endocrinología Molecular, Research Division, Hospital Juárez de México, Mexico City, Mexico.
Laboratorio de Bioquímica Farmacológica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
Front Genet. 2022 Jan 27;12:794476. doi: 10.3389/fgene.2021.794476. eCollection 2021.
The 5α-reductase type 2 deficiency (5α-RD2) is a specific form of disorder of sexual development (DSD). Pathogenic variants in the gene, which encodes this enzyme, are responsible for 46,XY DSD. The objective of the study was to investigate the genetic etiology of 46,XY DSD in two Mexican families with affected children. The gene of the parents and affected children was screened in both families polymerase chain reaction amplification and DNA direct sequencing. The role of genetic variants in enzymatic activity was tested by site-directed mutagenesis. Subject 1 presented two variants: p.Glu197Asp and p.Pro212Arg. Subject 2 was homozygous for the variant p.Glu197Asp. The two variants were reported in early studies. The directed mutagenesis study showed that the p.Glu197Asp and p.Pro212Arg variants lead to a total loss of enzymatic activity and, consequently, abnormal genitalia development in the patients. These results suggest that p.Glu197Asp and p.Pro212Arg are pathogenic variants that lead to the phenotypic expression of DSD. 5α-RD2 is of extreme importance not only because of its frequency (it is rare) but also because of its significance in understanding the mechanism of androgen action, the process of sexual differentiation, and the factors that influence normal sexual behavior.
2型5α-还原酶缺乏症（5α-RD2）是性发育障碍（DSD）的一种特殊形式。编码这种酶的基因中的致病变异导致46,XY DSD。本研究的目的是调查两个有患病儿童的墨西哥家庭中46,XY DSD的遗传病因。通过聚合酶链反应扩增和DNA直接测序对两个家庭中父母和患病儿童的该基因进行了筛查。通过定点诱变测试了基因变异在酶活性中的作用。受试者1出现了两个变异：p.Glu197Asp和p.Pro212Arg。受试者2是p.Glu197Asp变异的纯合子。这两个变异在早期研究中已有报道。定点诱变研究表明，p.Glu197Asp和p.Pro212Arg变异导致酶活性完全丧失，从而导致患者生殖器发育异常。这些结果表明，p.Glu197Asp和p.Pro212Arg是导致DSD表型表达的致病变异。5α-RD2不仅因其发病率（罕见），而且因其在理解雄激素作用机制、性分化过程以及影响正常性行为的因素方面的重要性而极为重要。
