Disruption of Contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome
Disruption of Contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome
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DOI：
10.1086/421474
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发表时间：
2004-06-01
影响因子：
9.8
通讯作者：
State, MW
中科院分区：
文献类型：
--
作者：
Fernandez, T;Morgan, T;State, MW
3 p缺失综合征是一种罕见的连续基因疾病，涉及3号染色体短臂端粒部分的缺失，并以发育迟缓、生长迟缓和畸形特征为特征。所有报道的病例都至少涉及3号染色体端粒到3p25.3带的缺失。尽管在这个区域中存在参与神经发育的几个基因，但特定转录本与观察到的临床表现之间的因果关系仍然难以捉摸。我们已经确定了一个孩子的特征性身体特征的3 p缺失综合征和语言和非语言发育迟缓谁携带从头平衡易位涉及染色体3和10。这种重排的精细作图表明，染色体3上的易位断裂点福尔斯落在最近鉴定的3 p缺失综合征的最小候选区域内，并破坏3p26.2-3p26.3处的接触蛋白4（CNTN 4）mRNA转录物。该转录物（也称为BIG-2）是参与中枢神经系统（CNS）中轴突生长、引导和成束的神经元细胞粘附分子的免疫球蛋白超家族的成员。我们的研究结果表明CNTN 4破坏与3 p缺失综合征表型的关联，并强烈表明因果关系。这些发现指出CNTN 4在正常和异常CNS发育中的重要作用。
3p deletion syndrome is a rare contiguous-gene disorder involving the loss of the telomeric portion of the short arm of chromosome 3 and characterized by developmental delay, growth retardation, and dysmorphic features. All reported cases have involved, at a minimum, the deletion of chromosome 3 telomeric to the band 3p25.3. Despite the presence of several genes in this region that are involved in neural development, a causative relationship between a particular transcript and the observed clinical manifestations has remained elusive. We have identified a child with characteristic physical features of 3p deletion syndrome and both verbal and nonverbal developmental delay who carries a de novo balanced translocation involving chromosomes 3 and 10. Fine mapping of this rearrangement demonstrates that the translocation breakpoint on chromosome 3 falls within the recently identified minimal candidate region for 3p deletion syndrome and disrupts the Contactin 4 (CNTN4) mRNA transcript at 3p26.2-3p26.3. This transcript (also known as BIG-2) is a member of the immunoglobulin super family of neuronal cell adhesion molecules involved in axon growth, guidance, and fasciculation in the central nervous system (CNS). Our results demonstrate the association of CNTN4 disruption with the 3p deletion syndrome phenotype and strongly suggest a causal relationship. These findings point to an important role for CNTN4 in normal and abnormal CNS development.