A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity
A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity
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DOI：
10.1002/ajmg.b.32406
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发表时间：
2016-03-01
影响因子：
2.8
通讯作者：
Brusco, Alfredo
中科院分区：
文献类型：
--
作者：
Biamino, Elisa;Di Gregorio, Eleonora;Brusco, Alfredo
拷贝数变异（CNV）与多种神经精神疾病相关，包括智力残疾/发育迟缓（ID/DD）、自闭症谱系障碍（ASD）和精神分裂症（SCZ）。通常，携带相同致病性CNV的个体表现出高临床变异性。通过阵列CGH分析，我们发现了一个新的家族性3q 29缺失（1.36Mb），位于3q 29缺失区的着丝粒，表现出可变的表达率。在一名被诊断患有ID/DD和自闭症的3岁女孩中发现了这种缺失，并将其隔离在6名家庭成员中，这些家庭成员都患有严重的精神疾病，包括精神分裂症，重度抑郁症，焦虑症和人格障碍。所有携带该缺失的个体均超重或肥胖，并且在四分之三的检查病例中观察到与视神经萎缩相容的异常。在缺失的10个基因中，与常染色体显性视神经萎缩相关的视神经萎缩1（OPA 1）的单倍不足可能是导致眼科异常的原因。我们推测ATP酶13 A4（ATP 13 A4）和/或分裂果蝇同源物1（HES 1）的Hairy/Enhancer的单倍不足导致神经精神表型，而HES 1的缺失可能是超重/肥胖的基础。总之，我们提出了一种新的连续基因综合征，由于近端3q 29缺失与自闭症，ID/DD，精神病特征和超重/肥胖。(c)2015年威利期刊公司
Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity. (c) 2015 Wiley Periodicals, Inc.