Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR
Details
Publication Year 2015-05-19,Volume 84,Issue #20,Page 2029-32
Journal Title
Neurology
Publication Type
Journal Article
Abstract
OBJECTIVE: To define causative somatic mutations in resected brain tissue from an infant with intractable epilepsy secondary to hemispheric cortical dysplasia. METHODS: Whole-exome sequencing was conducted on genomic DNA derived from both resected brain tissue and peripheral blood leukocytes. Comparison of the brain vs blood sequencing results was performed using bioinformatic methods designed to detect low-frequency genetic variation between tissue pairs. RESULTS: Histopathology of the resected tissue showed dyslamination and dysmorphic neurons, but no balloon cells, consistent with focal cortical dysplasia type IIa. mTOR activation was observed by immunohistochemistry in the dysplasia. A missense mutation (c.4487T>G; p.W1456G) was detected in the FAT domain of MTOR in DNA from the dysplasia but not in lymphocytes. The mutation is predicted damaging (i.e., leading to mTOR activation) and was observed as a low-level mosaic with 8% of cells being heterozygous for the variant. CONCLUSIONS: We report the novel finding of an MTOR mutation associated with nonsyndromic cortical dysplasia. Somatic-specific mutations in MTOR and related genes should be considered in a broader spectrum of patients with hemispheric malformations and more restricted forms of cortical dysplasia.
Publisher
American Academy of Neurology
Research Division(s)
Population Health And Immunity
PubMed ID
25878179
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-05-20 10:11:23
Last Modified: 2019-04-01 09:08:14
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