title: Mutations in BRAT1 cause autosomal recessive progressive encephalopathy: Report of a Spanish patient.
abstract: We describe a 4-year-old male child born to non-consanguineous Spanish parents with progressive encephalopathy (PE), microcephaly, and hypertonia. Whole exome sequencing revealed compound heterozygous BRAT1 mutations [c.1564G > A (p.Glu522Lys) and c.638dup (p.Val214Glyfs*189)]. Homozygous and compound heterozygous BRAT1 mutations have been described in patients with lethal neonatal rigidity and multifocal seizure syndrome (MIM# 614498). The seven previously described patients suffered from uncontrolled seizures, and all of those patients died in their first months of life. BRAT1 acts as a regulator of cellular proliferation and migration and is required for mitochondrial function. The loss of these functions may explain the cerebral atrophy observed in this case of PE. This case highlights the extraordinary potential of next generation technologies for the diagnosis of rare genetic diseases, including PE. Making a prompt diagnosis of PE is important for genetic counseling and disease management.
authors.affiliation: Department of Pediatric Neurology, Hospital Universitario Quirón, Madrid, Spain. Electronic address: aferjaen@telefonica.net.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Jaén
authors.affiliation: Genomics and Medicine, NIMGenetics, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Álvarez
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Eui Young
authors.initials: EY
authors.lastname: So
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Toru
authors.initials: T
authors.lastname: Ouchi
authors.affiliation: Neuro-Radiology Unit, Magnetic Resonance Unit, Hospital Universitario Quirón, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Jiménez de la Peña
authors.affiliation: Pediatric Neurology Unit, Hospital Universitario Niño Jesús, Madrid, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Duat
authors.affiliation: Department of Pediatric Neurology, Hospital Universitario Quirón, Madrid, Spain.
authors.forename: Daniel Martín
authors.initials: DM
authors.lastname: Fernández-Mayoralas
authors.affiliation: Department of Pediatric Neurology, Hospital Universitario Quirón, Madrid, Spain.
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Fernández-Perrone
authors.affiliation: Department of Biological and Health Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, Spain.
authors.forename: Jacobo
authors.initials: J
authors.lastname: Albert
authors.affiliation: Pediatric Primary Care, C. S. Doctor Cirajas, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Calleja-Pérez
mesh_terms: D002648:Child; D006579:Heterozygote; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012640:Seizures / Q000235:genetics*
chemical_list: C573230:BRAT1 protein, human; D009687:Nuclear Proteins
keywords: BRAT1; Lethal neonatal rigidity; Progressive encephalopathy; Whole exome sequencing