title: Homozygous mutation in PRUNE1 in an Oji-Cree male with a complex neurological phenotype.
abstract: The PRUNE1 gene encodes a member of the phosphoesterases (DHH) protein superfamily that is highly expressed in the human fetal brain and involved in the regulation of cell migration. Homozygous or compound heterozygous PRUNE1 mutations were recently identified in five individuals with brain malformations from four families. We present a case of a 2-year-old male with a complex neurological phenotype and abnormalities on brain MRI. Re-annotation of clinical whole-exome sequencing data revealed a homozygous likely pathogenic variant in PRUNE1 (c.521-2A>G). These results further delineate a new PRUNE1-related syndrome, and highlight the importance of periodic data re-annotation in individuals who remain without a diagnosis after undergoing genome-wide testing. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Medical Genetics Residency Training Program, University of Toronto, Ontario, Canada.|Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario, Canada.
authors.forename: Gregory
authors.initials: G
authors.lastname: Costain
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Ontario, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Shugar
authors.affiliation: Department of Diagnostic Imaging, The Hospital for Sick Children, Ontario, Canada.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Krishnan
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario, Canada.
authors.forename: Saadet
authors.initials: S
authors.lastname: Mahmutoglu
authors.affiliation: Department of Diagnostic Imaging, The Hospital for Sick Children, Ontario, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Laughlin
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario, Canada.|Institute of Medical Sciences, University of Toronto, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Kannu
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D002874:Chromosome Mapping; D059472:Exome; D019066:Facies; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010641:Phenotype
keywords: Cree; DRES17; HTCD37; Ojibwe; PRUNE; PRUNE1; brain structure; founder effect; infantile spasms; whole-exome sequencing