Prader-Willi综合征下丘脑功能障碍的遗传机制研究进展

doi:10.16288/j.yczz.22-188

遗传 ›› 2022, Vol. 44 ›› Issue (10): 899-912.doi: 10.16288/j.yczz.22-188

Prader-Willi综合征下丘脑功能障碍的遗传机制研究进展

王心缘(), 孙睿, 高原青()

南京医科大学药学院,江苏省心脑血管药物重点实验室,南京 211166

收稿日期:2022-06-30 修回日期:2022-07-28 出版日期:2022-10-20 发布日期:2022-08-11
通讯作者: 高原青 E-mail:darlingxyxy@163.com;yuanqinggao@njmu.edu.cn
作者简介:王心缘,在读硕士研究生,专业方向：药理学。E-mail: darlingxyxy@163.com
基金资助:
国家自然科学基金项目(81873654)

Advances in genetic mechanisms of hypothalamic dysfunction in Prader-Willi syndrome

Xinyuan Wang(), Rui Sun, Yuanqing Gao()

Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China

Received:2022-06-30 Revised:2022-07-28 Online:2022-10-20 Published:2022-08-11
Contact: Gao Yuanqing E-mail:darlingxyxy@163.com;yuanqinggao@njmu.edu.cn
Supported by:
the National Natural Science Foundation of China(81873654)

摘要/Abstract

摘要：

Prader-Willi 综合征(Prader-Willi syndrome, PWS)是一种罕见的先天发育性疾病,主要由父系15号染色体长臂15q11~q13区域基因缺失或沉默引起。PWS临床表型复杂,主要包括无法满足的饥饿、病态的肥胖、智力发育迟缓、性腺发育不良等,多数症状提示与下丘脑的功能障碍相关。然而到目前为止,PWS的分子遗传机制尚不明确,尤其是基因和临床表现之间的对应关系和详细机制有待进一步研究。本文以PWS“基因型-下丘脑功能障碍表型”之间的关联为重点,综述了15q11~q13区域基因(NIPA1、NIPA2、TUBGCP5、CYFIP1、MAGEL2、NDN、MKRN3和SNORD116等)与PWS患者过度摄食和肥胖、性腺发育不良、睡眠呼吸障碍、生长发育迟缓等表型相关的研究进展,旨在加深对PWS遗传机制的理解,探讨潜在的PWS药物靶点的可能性。

关键词: Prader-Willi 综合征, 下丘脑, 遗传机制

Abstract:

Prader-Willi syndrome (PWS) is a rare congenital developmental disorder mainly due to the absent expression of genes on the paternally inherited chromosome 15q11-q13 region. Most of the clinical symptoms of PWS are related to hypothalamic dysfunction, including hyperphagia, morbid obesity, mental retardation, and hypogonadism. However, the molecular genetic mechanism of PWS is not fully understood, especially the relationship between genotype and phenotype. In this review, we focus on the genetic mechanisms behind the hypothalamus dysfunction, summarizing the latest research progress of the roles of PWS candidate genes in chromosome 15q11-q13 region (NIPA1, NIPA2, TUBGCP5, CYFIP1, MAGEL2, NDN, MKRN3 and SNORD116) in hypothalamic disorders such as hyperphagia and obesity, hypogonadism, sleep-disordered breathing, growth retardation in PWS patients, to deepen the understanding of PWS syndrome and explore potential new drug targets.

Key words: Prader-Willi syndrome, hypothalamus, genetic mechanism

王心缘, 孙睿, 高原青. Prader-Willi综合征下丘脑功能障碍的遗传机制研究进展[J]. 遗传, 2022, 44(10): 899-912.

Xinyuan Wang, Rui Sun, Yuanqing Gao. Advances in genetic mechanisms of hypothalamic dysfunction in Prader-Willi syndrome[J]. Hereditas(Beijing), 2022, 44(10): 899-912.

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基因分组	基因	下丘脑功能障碍表型	参与的生物过程/机制	参考文献
近端非印记区	NIPA1	食欲亢进、过度摄食	镁离子转运蛋白,调控神经元的分泌和吞噬	[36~38]
	NIPA2	生长发育迟缓、骨质疏松	镁离子转运蛋白,调控神经元的分泌和吞噬、影响神经元兴奋性;调节线粒体自噬	[39,40,41,42]
	TUBGCP5	神经发育迟缓;行为问题	细胞分裂过程	[43~45]
	CYFIP1	生长发育迟缓、智力障碍;强迫性摄食行为	调节细胞骨架动力学和蛋白质翻译,影响轴突生长和突触功能	[46,47,48,49,50,51,52,53]
PWS仅父系表达印记区	MKRN3	性腺功能减退	调控GnRH的分泌,影响下丘脑-垂体-性腺轴	[54,55,56,57,58,59]
	MAGEL2	新生儿喂养困难;过度摄食与肥胖;昼夜节律失调;性腺功能减退	影响神经肽的产生及分泌,调控轴突生长、突触功能等	[60,61,62,63,64,65,66,67,68,68,69,70,71,72,73,74]
	NDN	睡眠呼吸功能障碍;学习行为异常;生殖功能改变	调控轴突的生长和迁移、神经元的分化和存活;调控时钟基因的表达,影响昼夜节律	[75,76,77,78,79,80,81,82,83,84,85,86,87,88]
	SNORD116	生长发育迟缓;过度摄食和肥胖;睡眠功能障碍	RNA修饰和剪接,调控摄食神经环路和昼夜节律	[89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105]
远端非印记区	HERC2	性腺功能减退;生长发育迟缓	蛋白质囊泡运输和降解途径	[106~108]
远端非印记区	GABA 受体亚基	过度摄食与肥胖;学习记忆障碍;强迫行为	调控中枢神经系统抑制性神经递质	[109~111]

Prader-Willi综合征下丘脑功能障碍的遗传机制研究进展

Advances in genetic mechanisms of hypothalamic dysfunction in Prader-Willi syndrome

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