出现青春期提前的 MC2R 缺乏症患者的临床和遗传机制。

IF 2.6 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Hormone Research in Paediatrics Pub Date : 2024-11-01 DOI:10.1159/000542307

Esin Karakilic Ozturan, Zehra Yavas Abali, Volkan Karaman, Sukran Poyrazoglu, Zehra Oya Uyguner, Feyza Darendeliler, Firdevs Bas

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引用次数: 0

摘要

简介肾上腺皮质中的黑色素皮质素受体 2（MC2R）控制着下丘脑-垂体-肾上腺轴。黑色素皮质素系统受瘦素的影响，可调节对青春期开始和生育至关重要的 GnRH 神经元。本研究评估了原发性肾上腺功能不全（PAI）患者因 MC2R 基因改变而导致的青春期提前：方法：研究纳入了来自五个非亲缘家庭的七名 PAI 患者（P1-P7），他们均表现为青春期提前或早熟。MC2R缺乏的诊断时间从1天到11个月不等。对四个病例（P2、P4、P6 和 P7）的 MKRN3、DLK1、KISS1 和 KISS1R 基因进行了桑格测序分析。所有临床数据均为回顾性获得：结果：男孩（P1、P2、P3、P7）的青春期发病平均年龄为 8.6 岁（7.4-9.5 岁），女孩（P4、P5、P6）的青春期发病平均年龄为 8.5 岁（7.4-9.5 岁）。肿瘤标志物呈阴性，未发现肾上腺休止期或肿瘤。P2、P3和P6使用GnRH类似物进行快速青春期发育。P1 和 P2 的最终身高低于目标值（-2.6 SDS、-0.7 SDS）。P4 和 P5 分别在 11 岁和 11.3 岁初潮。未发现致病变异：结论：未发现青春期提前的遗传原因。升高的促肾上腺皮质激素可能会刺激吻肽神经元，引发青春期。建议密切监测这些患者的青春期发育情况。

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Clinical and Genetic Mechanisms in Patients with MC2R Deficiency Presenting with Early Puberty.

Introduction: Melanocortin receptor 2 (MC2R) in the adrenal cortex controls the hypothalamic-pituitary-adrenal axis. The melanocortin system, influenced by leptin, regulates GnRH neurons, crucial for puberty onset and fertility. This study evaluates early puberty in primary adrenal insufficiency (PAI) patients due to MC2R gene alterations.

Methods: Seven patients with PAI (P1-P7) from five unrelated families, all presenting with early or precocious puberty, were included. MC2R deficiency diagnosis ranged from 1 day to 11 months. MKRN3, DLK1, KISS1, and KISS1R genes were analyzed using Sanger sequencing in four cases (P2,P4,P6 and P7). All clinical data were obtained retrospectively.

Results: Puberty onset mean age was 8.6 years (7.4-9.5) in boys (P1, P2, P3, P7) and 8.5 years (7.4-9.5) in girls (P4, P5, P6). Tumor markers were negative; no adrenal rest or tumors were found. GnRH analogs were used for rapid puberty in P2, P3, P6. Final height in P1 and P2 was below target (-2.6 SDS, -0.7 SDS). Menarche occurred at 11 and 11.3 years in P4 and P5. No pathogenic variants were found.

Conclusion: Genetic causes of early puberty were not identified. Elevated ACTH may stimulate kisspeptin neurons, triggering puberty. Close monitoring of these patients for pubertal development is recommended.

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来源期刊

Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS

CiteScore

4.90

自引率

6.20%

发文量

审稿时长

4-8 weeks

期刊介绍： The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.