两例CNTN6拷贝数变异患者的临床和分子特征。

PubMed ID
发表日期 2018年月

原始出处 细胞遗传学与基因组研究
Cytogenetic and genome research
作者 Tassano  Elisa  Uccella  Sara  Giacomini  Thea  Severino  Mariasavina  Fiorio  Patrizia  Gimelli  Giorgio  Ronchetto  Patrizia 

文献标题 两例CNTN6拷贝数变异患者的临床和分子特征。
Clinical and Molecular Characterization of Two Patients with CNTN6 Copy Number Variations.

文献摘要

亚显微染色体改变通常涉及不同的蛋白质编码基因和调控元件,这些基因和调控元件导致罕见的相邻基因疾病,这使得对基因型-表型相关性的理解复杂化。染色体带3p26.3包含3个编码神经细胞粘附分子的基因:CHL1、CNTN6和CNTN4。我们描述了2名8岁和11岁的男孩,他们主要受智力残疾和孤独症谱系障碍的影响,他们分别有一个父亲遗传的3p26.3微缺失和一个3p26.3微重复。这两种异常仅涉及CNTN6基因,该基因编码contactin 6,contactin家族的一员(MIM 607220)。接触蛋白表现出明显的大脑表达和功能。有趣的是,CNTN6相互微缺失和微复制的表型非常相似。总之,我们的数据,加上那些在文献中报道的,对于理解单基因剂量改变的致病作用是特别重要的。至于其他具有可变表型的复发综合征,这些发现在遗传咨询中具有挑战性,因为明显的可变外显率。


Submicroscopic chromosomal alterations usually involve different protein-coding genes and regulatory elements that are responsible for rare contiguous gene disorders, which complicate the understanding of genotype-phenotype correlations. Chromosome band 3p26.3 contains 3 genes encoding neuronal cell adhesion molecules: CHL1, CNTN6, and CNTN4. We describe 2 boys aged 8 years and 11 years mainly affected by intellectual disability and autism spectrum disorder, who harbor a paternally inherited 3p26.3 microdeletion and a 3p26.3 microduplication, respectively. Both anomalies involved only the CNTN6 gene, which encodes contactin 6, a member of the contactin family (MIM 607220). Contactins show pronounced brain expression and function. Interestingly, phenotypes in reciprocal microdeletions and microduplications of CNTN6 are very similar. In conclusion, our data, added to those reported in the literature, are particularly significant for understanding the pathogenic effect of single gene dosage alterations. As for other recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance.


获取全文 10.1159/000494152