title: Functional characterization of a GFAP variant of uncertain significance in an Alexander disease case within the setting of an individualized medicine clinic.
abstract: A de novo GFAP variant, p.R376W, was identified in a child presenting with hypotonia, developmental delay, and abnormal brain MRI. Following the 2015 ACMG variant classification guidelines and the functional studies showing protein aggregate formation in vitro, p.R376W should be classified as a pathogenic variant, causative for Alexander disease.
authors.affiliation: Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Boczek
authors.affiliation: Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA; Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota USA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Sigafoos
authors.affiliation: Department of Biomedical Informatics Mayo Clinic Rochester Minnesota USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Zimmermann
authors.affiliation: Mayo Graduate School and the Department of Immunology Mayo Clinic Rochester Minnesota USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Maus
authors.affiliation: Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA.
authors.forename: Margot A
authors.initials: MA
authors.lastname: Cousin
authors.affiliation: Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Blackburn
authors.affiliation: Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota USA; Department of Biophysics and Medicine Mayo Clinic Rochester Minnesota USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Urrutia
authors.affiliation: Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA; Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota USA.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Clark
authors.affiliation: Department of Clinical Genomics Mayo Clinic Rochester Minnesota USA; Departments of Neurology and Pediatrics Mayo Clinic Rochester Minnesota USA.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Patterson
authors.affiliation: Department of Clinical Genomics Mayo Clinic Rochester Minnesota USA; Department of Obstetrics and Gynecology Mayo Clinic Rochester Minnesota USA.
authors.forename: Myra J
authors.initials: MJ
authors.lastname: Wick
authors.affiliation: Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA; Department of Biomedical Informatics Mayo Clinic Rochester Minnesota USA; Department of Clinical Genomics Mayo Clinic Rochester Minnesota USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
keywords: Alexander disease; developmental delay disorders; glial fibrillary acid protein; leukoencephalopathies; muscle hypotonia; paralog analysis