Copy number variants are frequent in genetic generalized epilepsy with intellectual disability
Neurology, 2013•AAN Enterprises
Objective: We examined whether copy number variants (CNVs) were more common in those
with a combination of intellectual disability (ID) and genetic generalized epilepsy (GGE) than
in those with either phenotype alone via a case-control study. Methods: CNVs contribute to
the genetics of multiple neurodevelopmental disorders with complex inheritance, including
GGE and ID. Three hundred fifty-nine probands with GGE and 60 probands with ID-GGE
were screened for GGE-associated recurrent microdeletions at 15q13. 3, 15q11. 2, and …
with a combination of intellectual disability (ID) and genetic generalized epilepsy (GGE) than
in those with either phenotype alone via a case-control study. Methods: CNVs contribute to
the genetics of multiple neurodevelopmental disorders with complex inheritance, including
GGE and ID. Three hundred fifty-nine probands with GGE and 60 probands with ID-GGE
were screened for GGE-associated recurrent microdeletions at 15q13. 3, 15q11. 2, and …
Objective
We examined whether copy number variants (CNVs) were more common in those with a combination of intellectual disability (ID) and genetic generalized epilepsy (GGE) than in those with either phenotype alone via a case-control study.
Methods
CNVs contribute to the genetics of multiple neurodevelopmental disorders with complex inheritance, including GGE and ID. Three hundred fifty-nine probands with GGE and 60 probands with ID-GGE were screened for GGE-associated recurrent microdeletions at 15q13.3, 15q11.2, and 16p13.11 via quantitative PCR or loss of heterozygosity. Deletions were confirmed by comparative genomic hybridization (CGH). ID-GGE probands also had genome-wide CGH.
Results
ID-GGE probands showed a significantly higher rate of CNVs compared with probands with GGE alone, with 17 of 60 (28%) ID-GGE probands having one or more potentially causative CNVs. The patients with ID-GGE had a 3-fold-higher rate of the 3 GGE-associated recurrent microdeletions than probands with GGE alone (10% vs 3%, p = 0.02). They also showed a high rate (13/60, 22%) of rare CNVs identified using genome-wide CGH.
Conclusions
This study shows that CNVs are common in those with ID-GGE with recurrent deletions at 15q13.3, 15q11.2, and 16p13.11, particularly enriched compared with individuals with GGE or ID alone. Recurrent CNVs are likely to act as risk factors for multiple phenotypes not just at the population level, but also in any given individual. Testing for CNVs in ID-GGE will have a high diagnostic yield in a clinical setting and will inform genetic counseling.
American Academy of Neurology以上显示的是最相近的搜索结果。 查看全部搜索结果