目的:NR5A1是性别分化的关键调节因子,通过TLX1的转录激活参与脾脏发育。由于NR5A1引起的疾病变异而存在性发育差异(DSD)的个体中存在对低脾或无脾的担忧。我们旨在评估此类个体的临床队列中的脾脏解剖结构和功能,以及无症状的家庭成员携带者。
方法:对来自18个家庭的22名DSD或原发性卵巢功能不全患者和5名无症状携带者进行横断面评估,藏有14种不同的NR5A1变体。
方法:通过超声评估脾脏解剖结构,脾功能通过外周血细胞计数,白细胞分化,非交换记忆B细胞的百分比,特异性肺炎球菌抗体反应,%的红血球和Howell-Jolly尸体。
结果:与健康对照相比,患者和无症状杂合个体的非转换记忆B细胞显著减少,但高于脾虚患者。50%的杂合个体存在血小板增多和脾发育不全。对于先前描述的p。(Arg103Gln)变体纯合的五个个体中有四个患有脾。
结论:携带可能导致DSD的杂合子NR5A1变异体有相当大的功能性脾功能亢进风险,无论他们的性腺表型。应该评估这些个体的脾功能,如果受影响或未知,建议预防以防止侵入性包膜细菌感染。与NR5A1变异相关的脾表型在纯合个体中更严重,至少对于p。(Arg103Gln)变体,与脾有关。
OBJECTIVE: NR5A1 is a key regulator of sex differentiation and has been implicated in spleen development through transcription activation of TLX1. Concerns exist about hypo- or asplenism in individuals who have a difference of sex development (DSD) due to an NR5A1 disease-causing variant. We aimed to assess spleen anatomy and function in a clinical cohort of such individuals and in their asymptomatic family member carriers.
METHODS: Cross-sectional assessment in 22 patients with a DSD or primary ovarian insufficiency and 5 asymptomatic carriers from 18 families, harboring 14 different NR5A1 variants.
METHODS: Spleen anatomy was assessed by ultrasound, spleen function by peripheral blood cell count, white blood cell differentiation, percentage of nonswitched memory B cells, specific pneumococcal antibody response, % pitted red blood cells, and Howell-Jolly bodies.
RESULTS: Patients and asymptomatic heterozygous individuals had significantly decreased nonswitched memory B cells compared to healthy controls, but higher than asplenic patients. Thrombocytosis and spleen hypoplasia were present in 50% of heterozygous individuals. Four out of 5 individuals homozygous for the previously described p.(Arg103Gln) variant had asplenia.
CONCLUSIONS: Individuals harboring a heterozygous NR5A1 variant that may cause DSD have a considerable risk for functional hyposplenism, irrespective of their gonadal phenotype. Splenic function should be assessed in these individuals, and if affected or unknown, prophylaxis is recommended to prevent invasive encapsulated bacterial infections. The splenic phenotype associated with NR5A1 variants is more severe in homozygous individuals and is, at least for the p.(Arg103Gln) variant, associated with asplenism.