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

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。

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.