Hereditary spastic paraplegia caused by the PLP1 'rumpshaker mutation'.
BACKGROUND
Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterised by progressive spasticity and weakness in the lower limbs. Mutations in PLP1 on the X chromosome cause spastic paraplegia type 2 (SPG2) or the allelic Pelizaeus-Merzbacher Disease (PMD). The PLP1 protein is a major myelin protein involved in stabilisation and maintenance of the myelin sheath. The function of the protein has been studied in the rumpshaker mouse, which is a model of SPG2/PMD.


OBJECTIVE
To characterise the phenotype of patients with the 'rumpshaker mutation.'


METHODS
A family with HSP caused by the 'rumpshaker mutation.'


RESULTS
The patients showed nystagmus during infancy and had early onset of HSP. They had normal cognition, and cerebral MRI showed relatively unspecific white matter abnormalities on T2 sequences without clear progression. Urinary urgency was reported among the female carriers. MRS of both patients showed increased myo-inositol in the white matter, while decreased N-acetylaspartate was found exclusively in the oldest patient. All evoked potential examinations were compatible with severe central demyelination, while no signs of peripheral demyelination or axonal degeneration were found. (18)F-FDG-PET scans were normal.


CONCLUSIONS
The phenotypes of the patients reported here are the mildest described to be caused by the rumpshaker mutation and represent the mildest form among the spectrum of PLP1 related disorders. No definite symptoms in the female carriers could be ascribed to the mutation. These data suggest the pathology to be an underlying dysmyelinating disorder in combination with a central axonal degeneration.
Svenstrup
Kirsten
K
Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark. ksvenstrup@sund.ku.dk
Giraud
Geneviève
G
Boespflug-Tanguy
Odile
O
Danielsen
Else R
ER
Thomsen
Carsten
C
Rasmussen
Kirsten
K
Law
Ian
I
Vogel
Asmus
A
Stokholm
Jette
J
Crone
Clarissa
C
Hjermind
Lena E
LE
Nielsen
Jørgen E
JE
D000368:Aged; D000483:Alleles; D041321:Chromosomes, Human, X / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005074:Evoked Potentials, Visual / Q000502:physiology; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D009483:Neuropsychological Tests; D020417:Nystagmus, Congenital; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D012720:Severity of Illness Index; D015419:Spastic Paraplegia, Hereditary / Q000453:epidemiology / Q000235:genetics*
D017931:DNA Primers; D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human