MKRN3 基因突变导致的中枢性性早熟患者经促性腺激素释放激素类似物治疗后的结局。
Outcomes of Patients with Central Precocious Puberty Due to Loss-of-Function Mutations in the MKRN3 Gene after Treatment with Gonadotropin-Releasing Hormone Analog.
机构信息
Unidade de Endocrinologia do Desenvolvimento, Disciplina de Endocrinologia e Metabologia da Faculdade de Medicina da Universidade de São Paulo e Laboratório de Hormônios e Genética Molecular LIM 42 do Hospital das Clínicas, São Paulo, Brazil,
Unidade de Endocrinologia do Desenvolvimento, Disciplina de Endocrinologia e Metabologia da Faculdade de Medicina da Universidade de São Paulo e Laboratório de Hormônios e Genética Molecular LIM 42 do Hospital das Clínicas, São Paulo, Brazil.
出版信息
Neuroendocrinology. 2020;110(7-8):705-713. doi: 10.1159/000504446. Epub 2019 Oct 31.
INTRODUCTION
Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown.
OBJECTIVE
To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated.
PATIENTS AND METHODS
Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH).
RESULTS
At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP.
CONCLUSION
Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults' life.
简介
MKRN3 的功能丧失性突变是家族性中枢性性早熟（CPP）最常见的遗传原因。MKRN3 缺陷的 CPP 患者接受促性腺激素释放激素类似物（GnRHa）治疗的效果尚不清楚。
目的
描述接受 GnRHa 治疗的 MKRN3 基因突变或无 MKRN3 基因突变的 CPP 患者的临床和激素特征。评估了人体测量学、代谢和生殖参数。
患者和方法
纳入了 29 名因 MKRN3 失活突变而患有 CPP 的女性患者和 43 名特发性 CPP 的女性患者。回顾性评估了他们在 GnRHa 治疗前、治疗期间和治疗后的临床、实验室和影像学研究。所有特发性 CPP 患者和 11 名因 MKRN3 缺陷而患有 CPP 的患者均达到最终身高（FH）。
结果
在诊断时，MKRN3 基因突变或无 MKRN3 基因突变的 CPP 患者的临床和实验室特征无显著差异。观察到患有 CPP 的患者超重和肥胖的发生率较高（MKRN3 突变组为 47.3%，无 MKRN3 突变组为 50%），GnRHa 治疗后显著降低。GnRHa 治疗后，MKRN3 突变组和无 MKRN3 突变组的平均 FH 和目标身高值无显著差异。MKRN3 突变组和无 MKRN3 突变组的初潮年龄分别为 11.5±1.3 岁和 12±0.6 岁，均在预期年龄。MKRN3 突变组的多囊卵巢综合征患病率为 9.1%，特发性 CPP 组为 5.9%。
结论
MKRN3 基因突变或无 MKRN3 基因突变的 CPP 患者接受 GnRHa 治疗后的人体测量学、代谢和生殖结局相当，表明 MKRN3 缺陷对年轻成年女性的生活没有有害影响。
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