title: Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis.
abstract: OBJECTIVE
  Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported.
  
  
  METHODS
  CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced.
  
  
  RESULTS
  One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS.
  
  
  CONCLUSIONS
  Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.
authors.affiliation: Department of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.|Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Christina
authors.initials: C
authors.lastname: Sundal
authors.affiliation: Department of Neurosciences and Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Virginija
authors.initials: V
authors.lastname: Karrenbauer
authors.affiliation: Department of Neurology, Oslo University Hospital, Ullevål and University of Oslo, Norway.
authors.forename: Marte
authors.initials: M
authors.lastname: Gustavsen
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sahl
authors.initials: S
authors.lastname: Bedri
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Glaser
authors.affiliation: KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Norway.|Norwegian MS Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Haugarvoll
authors.affiliation: Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.|UCL Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Neurology, Oslo University Hospital, Ullevål and University of Oslo, Norway.
authors.forename: Hanne
authors.initials: H
authors.lastname: Harbo
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.affiliation: Department of Neurosciences and Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Wszolek
authors.affiliation: Department of Neurosciences and Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.affiliation: Department of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Oluf
authors.initials: O
authors.lastname: Andersen
mesh_terms: D000328:Adult; D005091:Exons; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009664:Norway; D010375:Pedigree; D010641:Phenotype; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D012042:Registries; D035781:Siblings; D013548:Sweden
chemical_list: D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: hereditary diffuse leukoencephalopathy with spheroids; white matter lesions