Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene.
Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene.
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DOI：
10.3390/diseases4010002
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发表时间：
2016-01-13
期刊：
影响因子：
--
通讯作者：
Schaaf CP
中科院分区：
文献类型：
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作者：
Fountain MD;Schaaf CP
Prader-Willi综合征（PWS）是一种神经发育障碍，其特征为新生儿张力减退、发育迟缓/智力残疾和婴儿期无法茁壮成长的特征性进食行为;随后在儿童期出现摄食过多和体重过度增加。患有PWS的个体也表现出复杂的行为表型。大约25%符合自闭症谱系障碍（ASD）的标准。PWS是由染色体15 q11-q13上父系表达、母系沉默的基因缺失引起的。MAGEL 2是PWS关键结构域中的五个蛋白质编码基因之一。MAGEL 2的父系等位基因的截断点突变导致Schaaf-Yang综合征，其与PWS具有显著的表型重叠，但在临床上也是不同的;基于关节挛缩的存在，以及自闭症谱系障碍的特别高的患病率（高达75%的受影响个体）。PWS和Schaaf-Yang综合征之间的临床和分子重叠，以及它们的区别特征，为深入了解这两种疾病的发病机制提供了依据。
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD). PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals). The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders.