title: Novel European SLC1A4 variant: infantile spasms and population ancestry analysis.
abstract: SLC1A4 deficiency is a recently described neurodevelopmental disorder associated with microcephaly, global developmental delay, abnormal myelination, thin corpus callosum and seizures. It has been mainly reported in the Ashkenazi-Jewish population with affected individuals homozygous for the p.Glu256Lys variant. Exome sequencing performed in an Irish proband identified a novel homozygous nonsense SLC1A4 variant [p.Trp453*], confirming a second case of SLC1A4-associated infantile spasms. As this is the first European identified, population ancestry analysis of the Exome Aggregation Consortium database was performed to determine the wider ethnic background of SLC1A4 deficiency carriers. p.Glu256Lys was found in Hispanic and South Asian populations. Other potential disease-causing variants were also identified. Investigation for SLC1A4 deficiency should be performed regardless of ethnicity and extend to include unexplained early-onset epileptic encephalopathy.
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.|Department of Child Neurology & Clinical Neurophysiology, Children's University Hospital, Dublin, Ireland.
authors.forename: Judith
authors.initials: J
authors.lastname: Conroy
authors.affiliation: Department of Child Neurology & Clinical Neurophysiology, Children's University Hospital, Dublin, Ireland.|Department of Paediatrics, National University of Ireland Galway, Galway University Hospital, Galway, Ireland.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Allen
authors.affiliation: Department of Child Neurology & Clinical Neurophysiology, Children's University Hospital, Dublin, Ireland.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gorman
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Eoghan
authors.initials: E
authors.lastname: O'Halloran
authors.affiliation: Department of Child Neurology & Clinical Neurophysiology, Children's University Hospital, Dublin, Ireland.
authors.forename: Amre
authors.initials: A
authors.lastname: Shahwan
authors.affiliation: Department of Child Neurology & Clinical Neurophysiology, Children's University Hospital, Dublin, Ireland.
authors.forename: Bryan
authors.initials: B
authors.lastname: Lynch
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Lynch
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Ennis
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.|Department of Child Neurology & Clinical Neurophysiology, Children's University Hospital, Dublin, Ireland.
authors.forename: Mary D
authors.initials: MD
authors.lastname: King
mesh_terms: D026962:Amino Acid Transport System ASC / Q000235:genetics*; D001921:Brain / Q000473:pathology; D003241:Consanguinity; D004569:Electroencephalography; D059472:Exome; D014644:Genetic Variation; D005828:Genetics, Population; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D013036:Spasms, Infantile / Q000175:diagnosis* / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D026962:Amino Acid Transport System ASC; C498848:SLC1A4 protein, human