Mutations in BRAT1 cause autosomal recessive progressive encephalopathy: Report of a Spanish patient

• Published in: European journal of paediatric neurology Vol. 20; no. 3; pp. 421 - 425
• Main Authors: Fernández-Jaén, Alberto, Álvarez, Sara, Young So, Eui, Ouchi, Toru, Jiménez de la Peña, Mar, Duat, Anna, Martín Fernández-Mayoralas, Daniel, Fernández-Perrone, Ana Laura, Albert, Jacobo, Calleja-Pérez, Beatriz
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2016
• Subjects: BRAT1; Child; Heterozygote; Humans; Lethal neonatal rigidity; Male; Microcephaly - genetics; Mutation - genetics; Neurology; Nuclear Proteins - genetics; Pediatrics; Progressive encephalopathy; Seizures - genetics; Whole exome sequencing; Progressive encephalopathy; Whole exome sequencing; BRAT1; Lethal neonatal rigidity
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/j.ejpn.2016.02.009

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.