Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder
Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder
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DOI：
10.1111/cge.12482
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发表时间：
2015-09-01
影响因子：
3.5
通讯作者：
Carter, M. T.
中科院分区：
文献类型：
--
作者：
Chaudhry, A.;Noor, A.;Carter, M. T.
对基因组拷贝数变异（CNV）的研究已经确定了与自闭症谱系障碍（ASD）和智力残疾（ID）相关的基因，如NRXN1，SHANK2，SHANK3和PTCHD1。在PTCHD 1中报告了缺失，但是关于这些个体的临床表现的信息很少。在此，我们提出了23个PTCHD1缺失或截短突变与详细的表型描述的个人。研究结果表明，PTCHD1编码区被破坏的个体可能具有细微的畸形特征，包括长脸、前额突出、眼睑浮肿和上唇薄。他们没有一致的相关先天性异常或生长异常模式。他们有轻度到中度的全面发展迟缓，不同程度的ID，许多人有突出的行为问题。超过40%的受试者有ASD或ASD样行为。在我们的队列中，唯一一致的神经学发现是口面肌张力减退和轻度运动不协调。我们的研究结果表明，半合子PTCHD1功能丧失导致X连锁神经发育障碍，具有强烈的自闭症行为倾向。需要详细的神经心理学研究来更好地定义认知和行为表型。
Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.