[MS9-4A-3] Large de novo microdeletion in children with epilepsy and intellectual and developmental disabilities, a systems biology analysis
Epilepsy is one of the most common neurological diseases. It is frequently associated with intellectual and developmental disabilities (ID/DD). In recent years, copy number variations (CNVs) were proven to be an important cause of epilepsy.
In this study, we performed a customized array comparative genomic hybridization (aCGH) to detect the CNVs in 96 Chinese epileptic patients with ID/DD. The aCGH was designed with a higher density probe coverage of 320 genes known to be involved in epilepsy and ID/DD with lower density whole-genome backbone coverage.
We identified 9 large de novo rare microdeletions in 8 patients. These CNVs are located on 2q24.1, 2q33.1-q34, 5q13.2 (2 similar CNVs), 5q33.1-q34, 17p13.2, 22q11.21-q11.22 (2 identical CNVs) and Xp22.31. We also found that only a few genes in the CNVs are known epilepsy related genes. By analysis with systems biological methods, we found most of the genes are interacting genes known to be epilepsy related genes. We also found a gene motif “BGNADP”, constructed by BTD, GALNT10, NMUR2, AUTS2, DLG2 and PTPRD, may be a key motif in epilepsy and ID/DD. These findings strongly indicate that some large de novo rare CNVs may be common pathological causes of epilepsy with ID/DD. Microdeletion of 5q13.2 and 17p13.2 was firstly found in patients of epilepsy with ID/DD. Our results suggested that a gene motif “BGNADP” may be a key network in epilepsy with ID/DD.
In this study, we performed a customized array comparative genomic hybridization (aCGH) to detect the CNVs in 96 Chinese epileptic patients with ID/DD. The aCGH was designed with a higher density probe coverage of 320 genes known to be involved in epilepsy and ID/DD with lower density whole-genome backbone coverage.
We identified 9 large de novo rare microdeletions in 8 patients. These CNVs are located on 2q24.1, 2q33.1-q34, 5q13.2 (2 similar CNVs), 5q33.1-q34, 17p13.2, 22q11.21-q11.22 (2 identical CNVs) and Xp22.31. We also found that only a few genes in the CNVs are known epilepsy related genes. By analysis with systems biological methods, we found most of the genes are interacting genes known to be epilepsy related genes. We also found a gene motif “BGNADP”, constructed by BTD, GALNT10, NMUR2, AUTS2, DLG2 and PTPRD, may be a key motif in epilepsy and ID/DD. These findings strongly indicate that some large de novo rare CNVs may be common pathological causes of epilepsy with ID/DD. Microdeletion of 5q13.2 and 17p13.2 was firstly found in patients of epilepsy with ID/DD. Our results suggested that a gene motif “BGNADP” may be a key network in epilepsy with ID/DD.