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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
SLC25A22 is a novel gene for migrating partial seizures in infancy
Annals of Neurology, Volume 74, No. 6, Year 2013
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Description
Objective To identify a genetic cause for migrating partial seizures in infancy (MPSI). Methods We characterized a consanguineous pedigree with MPSI and obtained DNA from affected and unaffected family members. We analyzed single nucleotide polymorphism 500K data to identify regions with evidence of linkage. We performed whole exome sequencing and analyzed homozygous variants in regions of linkage to identify a candidate gene and performed functional studies of the candidate gene SLC25A22. Results In a consanguineous pedigree with 2 individuals with MPSI, we identified 2 regions of linkage, chromosome 4p16.1-p16.3 and chromosome 11p15.4-pter. Using whole exome sequencing, we identified 8 novel homozygous variants in genes in these regions. Only 1 variant, SLC25A22 c.G328C, results in a change of a highly conserved amino acid (p.G110R) and was not present in control samples. SLC25A22 encodes a glutamate transporter with strong expression in the developing brain. We show that the specific G110R mutation, located in a transmembrane domain of the protein, disrupts mitochondrial glutamate transport. Interpretation We have shown that MPSI can be inherited and have identified a novel homozygous mutation in SLC25A22 in the affected individuals. Our data strongly suggest that SLC25A22 is responsible for MPSI, a severe condition with few known etiologies. We have demonstrated that a combination of linkage analysis and whole exome sequencing can be used for disease gene discovery. Finally, as SLC25A22 had been implicated in the distinct syndrome of neonatal epilepsy with suppression bursts on electroencephalogram, we have expanded the phenotypic spectrum associated with SLC25A22. Ann Neurol 2013;74:873-882 © 2013 American Neurological Association.
Authors & Co-Authors
Poduri, Annapurna H.
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
Heinzen, Erin L.
United States, Durham
Duke University School of Medicine
Chitsazzadeh, Vida
United States, Houston
University of Texas Medical School at Houston
Lasorsa, Francesco Massimo
Italy, Bari
Università Degli Studi Di Bari Aldo Moro
Italy, Rome
Consiglio Nazionale Delle Ricerche
Elhosary, Princess Christina
United States, Boston
Boston Children's Hospital
LaCoursiere, Christopher Mark
United States, Boston
Boston Children's Hospital
Martin, Emilie
United States, Boston
Boston Children's Hospital
Yuskaitis, Christopher J.
United States, Boston
Boston Children's Hospital
Hill, Robert Sean
United States, Boston
Boston Children's Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Atabay, Kutay Deniz
United States, Boston
Boston Children's Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Barry, Brenda J.
United States, Boston
Boston Children's Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Partlow, Jennifer Neil
United States, Boston
Boston Children's Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Bashiri, Fahad A.
Saudi Arabia, Riyadh
King Saud University
Zeidan, Radwan M.
Saudi Arabia, Riyadh
King Khalid University Hospital
Elmalik, Salah A.
Saudi Arabia, Riyadh
College of Medicine
Kabiraj, Mohammad Muslim Uddin
Saudi Arabia, Riyadh
Riyadh Military Hospital
Kothare, Sanjeev
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
Stödberg, Tommy I.
Sweden, Stockholm
Karolinska Universitetssjukhuset
McTague, Amy
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Kurian, M.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Scheffer, Ingrid E.
Australia, Melbourne
University of Melbourne
Barkovich, Anthony James
United States, San Francisco
University of California, San Francisco
Palmieri, Ferdinando
Italy, Bari
Università Degli Studi Di Bari Aldo Moro
Italy, Rome
Consiglio Nazionale Delle Ricerche
Salih, Mustafa Abdalla M.
Saudi Arabia, Riyadh
King Saud University
Walsh, Christopher A.
United States, Boston
Harvard Medical School
United States, Boston
Boston Children's Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 115
Authors: 25
Affiliations: 16
Identifiers
Doi:
10.1002/ana.23998
ISSN:
03645134
e-ISSN:
15318249
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health