title: Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations.
abstract: Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age-matched controls. The parallel (λ// ), perpendicular (λ⊥ ), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥ . In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥ . These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ// , are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.
authors.affiliation: Department of Neuroscience, University of Toledo, Toledo, Ohio; Center of Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Laukka
authors.forename: Malek I
authors.initials: MI
authors.lastname: Makki
authors.forename: Tori
authors.initials: T
authors.lastname: Lafleur
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stanley
authors.forename: John
authors.initials: J
authors.lastname: Kamholz
authors.forename: James Y
authors.initials: JY
authors.lastname: Garbern
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D065850:Cerebral Peduncle / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology; D056324:Diffusion Tensor Imaging; D004185:Disability Evaluation; D006801:Humans; D020772:Internal Capsule / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics* / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: CNS; DT-MRI; Pelizaeus-Merzbacher disease; myelin