RT Journal Article
SR Electronic
T1 Adult-Onset Alexander Disease: New Causal Sequence Variant in the GFAP Gene
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e681
DO 10.1212/NXG.0000000000000681
VO 8
IS 3
A1 Goerttler, Tsepo
A1 Zanetti, Letizia
A1 Regoni, Maria
A1 Egger, Karl
A1 Kellner, Elias
A1 Deuschl, Cornelius
A1 Kleinschnitz, Christoph
A1 Sassone, Jenny
A1 Klebe, Stephan
YR 2022
UL http://ng.neurology.org/content/8/3/e681.abstract
AB Objectives Alexander disease (AD) is a rare disorder of the CNS. Diagnosis is based on clinical symptoms, typical MRI findings, and mutations in the glial fibrillary acid protein (GFAP) gene. In this case study, we describe a new mutation (p.L58P) in GFAP that caused a phenotype of adult-onset AD (AOAD).Methods In our outpatient clinic, a patient presented with cerebellar and bulbar symptoms after brain concussion. We used MRI and performed next-generation exome sequencing (NGS) to find mutations in GFAP to diagnose AD. The mutation was then transfected into HeLa cell lines to prove its pathogenicity.Results The brain MRI finding showed typical AD alterations. The NGS found a heterozygous variant of unknown significance in GFAP (c.173T>C; p.L58P). After transfecting HeLa cell lines with this mutation, we showed that GFAP-L58P formed pathogenic clusters of cytoplasmic aggregates.Discussion We have found a new mutation that causes AOAD. We recommend that AOAD is included in the diagnostic workup in adult patients with gait ataxia and cerebellar and bulbar symptoms in association with a traumatic head injury.