PDF(Pubmed)
Abstract：
BACKGROUND: 46,XY sex reversal 11 (SRXY11) [OMIM#273250] is characterized by genital ambiguity that may range from mild male genital defects to gonadal sex reversal in severe cases. DHX37 is an RNA helicase that has recently been reported as a cause of SRXY11. So far, a total of 21 variants in DHX37 have been reported in 58 cases with 46,XY disorders of sex development (DSD).
METHODS: Whole exome sequencing (WES) was conducted to screen for variations in patients with 46,XY DSD. The subcellular localization of mutant DHX37 proteins was detected by immunofluorescence. And the levels of mutant DHX37 proteins were detected via Western blotting.
RESULTS: A novel pathogenic variant of DHX37 was identified in a patient with 46,XY DSD c.2012G > C (p.Arg671Thr). Bioinformatics analysis showed that the protein function of the variant was impaired. Compared with the structure of the wild-type DHX37 protein, the number of hydrogen bonds and interacting amino acids of the variant protein were changed to varying degrees. In vitro assays revealed that the variant had no significant effect on the intracellular localization of the protein but significantly reduced the expression level of the protein.
CONCLUSIONS: Our finding further expands the spectrum of the DHX37 variant and could assist in the molecular diagnosis of 46,XY DSD patients.
METHODS: Whole exome sequencing (WES) was conducted to screen for variations in patients with 46,XY DSD. The subcellular localization of mutant DHX37 proteins was detected by immunofluorescence. And the levels of mutant DHX37 proteins were detected via Western blotting.
RESULTS: A novel pathogenic variant of DHX37 was identified in a patient with 46,XY DSD c.2012G > C (p.Arg671Thr). Bioinformatics analysis showed that the protein function of the variant was impaired. Compared with the structure of the wild-type DHX37 protein, the number of hydrogen bonds and interacting amino acids of the variant protein were changed to varying degrees. In vitro assays revealed that the variant had no significant effect on the intracellular localization of the protein but significantly reduced the expression level of the protein.
CONCLUSIONS: Our finding further expands the spectrum of the DHX37 variant and could assist in the molecular diagnosis of 46,XY DSD patients.
摘要：
背景：46，XY性别逆转11（SRXY11）[OMIM＃273250]的特征是生殖器歧义，其范围可能从轻度的男性生殖器缺陷到严重的性腺性逆转。DHX37是一种RNA解旋酶，最近被报道为SRXY11的病因。到目前为止,在58例46,XY性发育障碍(DSD)患者中,已报告DHX37共有21种变异.
方法：进行全外显子组测序（WES）以筛选46,XYDSD患者的变异。通过免疫荧光检测突变型DHX37蛋白的亚细胞定位。并通过蛋白质印迹法检测突变型DHX37蛋白的水平。
结果：在46，XYDSDc.2012G>C的患者中发现了DHX37的一种新型致病变体（p。Arg671Thr）。生物信息学分析表明，该变体的蛋白质功能受损。与野生型DHX37蛋白的结构相比，变异蛋白的氢键数量和相互作用的氨基酸发生了不同程度的变化。体外测定显示该变体对蛋白质的细胞内定位没有显着影响，但显着降低了蛋白质的表达水平。
结论：我们的发现进一步扩展了DHX37变体的范围，可以帮助46，XYDSD患者的分子诊断。
方法：进行全外显子组测序（WES）以筛选46,XYDSD患者的变异。通过免疫荧光检测突变型DHX37蛋白的亚细胞定位。并通过蛋白质印迹法检测突变型DHX37蛋白的水平。
结果：在46，XYDSDc.2012G>C的患者中发现了DHX37的一种新型致病变体（p。Arg671Thr）。生物信息学分析表明，该变体的蛋白质功能受损。与野生型DHX37蛋白的结构相比，变异蛋白的氢键数量和相互作用的氨基酸发生了不同程度的变化。体外测定显示该变体对蛋白质的细胞内定位没有显着影响，但显着降低了蛋白质的表达水平。
结论：我们的发现进一步扩展了DHX37变体的范围，可以帮助46，XYDSD患者的分子诊断。
