PT  - JOURNAL ARTICLE
AU  - Nam Suk Sim
AU  - Youngsuk Seo
AU  - Jae Seok Lim
AU  - Woo Kyeong Kim
AU  - Hyeonju Son
AU  - Heung Dong Kim
AU  - Sangwoo Kim
AU  - Hyun Joo An
AU  - Hoon-Chul Kang
AU  - Se Hoon Kim
AU  - Dong-Seok Kim
AU  - Jeong Ho Lee
TI  - Brain somatic mutations in <em>SLC35A2</em> cause intractable epilepsy with aberrant N-glycosylation
AID  - 10.1212/NXG.0000000000000294
DP  - 2018 Dec 01
TA  - Neurology Genetics
PG  - e294
VI  - 4
IP  - 6
4099  - http://ng.neurology.org/content/4/6/e294.short
4100  - http://ng.neurology.org/content/4/6/e294.full
SO  - Neurol Genet2018 Dec 01; 4
AB  - Objective To identify whether somatic mutations in SLC35A2 alter N-glycan structures in human brain tissues and cause nonlesional focal epilepsy (NLFE) or mild malformation of cortical development (mMCD).Methods Deep whole exome and targeted sequencing analyses were conducted for matched brain and blood tissues from patients with intractable NLFE and patients with mMCD who are negative for mutations in mTOR pathway genes. Furthermore, tissue glyco-capture and nanoLC/mass spectrometry analysis were performed to examine N-glycosylation in affected brain tissue.Results Six of the 31 (19.3%) study patients exhibited brain-only mutations in SLC35A2 (mostly nonsense and splicing site mutations) encoding a uridine diphosphate (UDP)-galactose transporter. Glycome analysis revealed the presence of an aberrant N-glycan series, including high degrees of N-acetylglucosamine, in brain tissues with SLC35A2 mutations.Conclusion Our study suggests that brain somatic mutations in SLC35A2 cause intractable focal epilepsy with NLFE or mMCD via aberrant N-glycosylation in the affected brain.FCDII=focal cortical dysplasia type II; HexNAc=N-acetyl glucosamine; HME=hemimegalencephaly; mMCD=mild malformation of cortical development; NLFE=nonlesional focal epilepsy; VAF=variant allele frequency; WES=whole exome sequencing