---
_id: '691'
abstract:
- lang: eng
text: "Background: Transport protein particle (TRAPP) is a multisubunit complex
that regulates membrane trafficking through the Golgi apparatus. The clinical
phenotype associated with mutations in various TRAPP subunits has allowed elucidation
of their functions in specific tissues. The role of some subunits in human disease,
however, has not been fully established, and their functions remain uncertain.\r\n\r\nObjective:
We aimed to expand the range of neurodevelopmental disorders associated with mutations
in TRAPP subunits by exome sequencing of consanguineous families.\r\n\r\nMethods:
Linkage and homozygosity mapping and candidate gene analysis were used to identify
homozygous mutations in families. Patient fibroblasts were used to study splicing
defect and zebrafish to model the disease.\r\n\r\nResults: We identified six individuals
from three unrelated families with a founder homozygous splice mutation in TRAPPC6B,
encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental
disorder characterised by microcephaly, epilepsy and autistic features, and showed
splicing defect. Zebrafish trappc6b morphants replicated the human phenotype,
displaying decreased head size and neuronal hyperexcitability, leading to a lower
seizure threshold.\r\n\r\nConclusion: This study provides clinical and functional
evidence of the role of TRAPPC6B in brain development and function."
article_processing_charge: No
article_type: original
author:
- first_name: Isaac
full_name: Marin Valencia, Isaac
last_name: Marin Valencia
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Anide
full_name: Johansen, Anide
last_name: Johansen
- first_name: Başak
full_name: Rosti, Başak
last_name: Rosti
- first_name: Mahmoud
full_name: Issa, Mahmoud
last_name: Issa
- first_name: Damir
full_name: Musaev, Damir
last_name: Musaev
- first_name: Gifty
full_name: Bhat, Gifty
last_name: Bhat
- first_name: Eric
full_name: Scott, Eric
last_name: Scott
- first_name: Jennifer
full_name: Silhavy, Jennifer
last_name: Silhavy
- first_name: Valentina
full_name: Stanley, Valentina
last_name: Stanley
- first_name: Rasim
full_name: Rosti, Rasim
last_name: Rosti
- first_name: Jeremy
full_name: Gleeson, Jeremy
last_name: Gleeson
- first_name: Farhad
full_name: Imam, Farhad
last_name: Imam
- first_name: Maha
full_name: Zaki, Maha
last_name: Zaki
- first_name: Joseph
full_name: Gleeson, Joseph
last_name: Gleeson
citation:
ama: Marin Valencia I, Novarino G, Johansen A, et al. A homozygous founder mutation
in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly
epilepsy and autistic features. Journal of Medical Genetics. 2018;55(1):48-54.
doi:10.1136/jmedgenet-2017-104627
apa: Marin Valencia, I., Novarino, G., Johansen, A., Rosti, B., Issa, M., Musaev,
D., … Gleeson, J. (2018). A homozygous founder mutation in TRAPPC6B associates
with a neurodevelopmental disorder characterised by microcephaly epilepsy and
autistic features. Journal of Medical Genetics. BMJ Publishing Group. https://doi.org/10.1136/jmedgenet-2017-104627
chicago: Marin Valencia, Isaac, Gaia Novarino, Anide Johansen, Başak Rosti, Mahmoud
Issa, Damir Musaev, Gifty Bhat, et al. “A Homozygous Founder Mutation in TRAPPC6B
Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy
and Autistic Features.” Journal of Medical Genetics. BMJ Publishing Group,
2018. https://doi.org/10.1136/jmedgenet-2017-104627.
ieee: I. Marin Valencia et al., “A homozygous founder mutation in TRAPPC6B
associates with a neurodevelopmental disorder characterised by microcephaly epilepsy
and autistic features,” Journal of Medical Genetics, vol. 55, no. 1. BMJ
Publishing Group, pp. 48–54, 2018.
ista: Marin Valencia I, Novarino G, Johansen A, Rosti B, Issa M, Musaev D, Bhat
G, Scott E, Silhavy J, Stanley V, Rosti R, Gleeson J, Imam F, Zaki M, Gleeson
J. 2018. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental
disorder characterised by microcephaly epilepsy and autistic features. Journal
of Medical Genetics. 55(1), 48–54.
mla: Marin Valencia, Isaac, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates
with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and
Autistic Features.” Journal of Medical Genetics, vol. 55, no. 1, BMJ Publishing
Group, 2018, pp. 48–54, doi:10.1136/jmedgenet-2017-104627.
short: I. Marin Valencia, G. Novarino, A. Johansen, B. Rosti, M. Issa, D. Musaev,
G. Bhat, E. Scott, J. Silhavy, V. Stanley, R. Rosti, J. Gleeson, F. Imam, M. Zaki,
J. Gleeson, Journal of Medical Genetics 55 (2018) 48–54.
date_created: 2018-12-11T11:47:57Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2025-04-15T07:50:28Z
day: '01'
department:
- _id: GaNo
doi: 10.1136/jmedgenet-2017-104627
external_id:
isi:
- '000418199800007'
pmid:
- '28626029'
intvolume: ' 55'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056005/
month: '01'
oa: 1
oa_version: Submitted Version
page: 48 - 54
pmid: 1
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
publication: Journal of Medical Genetics
publication_identifier:
issn:
- 0022-2593
publication_status: published
publisher: BMJ Publishing Group
publist_id: '7016'
quality_controlled: '1'
scopus_import: '1'
status: public
title: A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental
disorder characterised by microcephaly epilepsy and autistic features
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 55
year: '2018'
...