Brain somatic mutations in SLC35A2 cause intractable epilepsy with aberrant N-glycosylation

Nam Suk Sim, Youngsuk Seo, Jae Seok Lim, Woo Kyeong Kim, Hyeonju Son, Heung Dong Kim, Sangwoo Kim, Hyun Joo An, Hoon Chul Kang, Se Hoon Kim, Dong Seok Kim, Jeong Ho Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere294
JournalNeurology: Genetics
Volume4
Issue number6
DOIs
Publication statusPublished - 2018 Dec 1

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Glycosylation
Partial Epilepsy
Mutation
Malformations of Cortical Development
Brain
Polysaccharides
Uridine Diphosphate Galactose
Exome
Acetylglucosamine
Drug Resistant Epilepsy
Mass Spectrometry
Genes

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Genetics(clinical)

Cite this

Sim, Nam Suk ; Seo, Youngsuk ; Lim, Jae Seok ; Kim, Woo Kyeong ; Son, Hyeonju ; Kim, Heung Dong ; Kim, Sangwoo ; An, Hyun Joo ; Kang, Hoon Chul ; Kim, Se Hoon ; Kim, Dong Seok ; Lee, Jeong Ho. / Brain somatic mutations in SLC35A2 cause intractable epilepsy with aberrant N-glycosylation. In: Neurology: Genetics. 2018 ; Vol. 4, No. 6.
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abstract = "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.",
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Brain somatic mutations in SLC35A2 cause intractable epilepsy with aberrant N-glycosylation. / Sim, Nam Suk; Seo, Youngsuk; Lim, Jae Seok; Kim, Woo Kyeong; Son, Hyeonju; Kim, Heung Dong; Kim, Sangwoo; An, Hyun Joo; Kang, Hoon Chul; Kim, Se Hoon; Kim, Dong Seok; Lee, Jeong Ho.

In: Neurology: Genetics, Vol. 4, No. 6, e294, 01.12.2018.

Research output: Contribution to journalArticle

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T1 - Brain somatic mutations in SLC35A2 cause intractable epilepsy with aberrant N-glycosylation

AU - Sim, Nam Suk

AU - Seo, Youngsuk

AU - Lim, Jae Seok

AU - Kim, Woo Kyeong

AU - Son, Hyeonju

AU - Kim, Heung Dong

AU - Kim, Sangwoo

AU - An, Hyun Joo

AU - Kang, Hoon Chul

AU - Kim, Se Hoon

AU - Kim, Dong Seok

AU - Lee, Jeong Ho

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

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.

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