G2Cdb::Human Disease report

Disease id
D00000213
Name
Spastic paraplegia type 2 (late onset)
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001806 PLP1
proteolipid protein 1
Y (10319897) Microinsertion (MI) Y

References

  • Novel exon 3B proteolipid protein gene mutation causing late-onset spastic paraplegia type 2 with variable penetrance in female family members.

    Sivakumar K, Sambuughin N, Selenge B, Nagle JW, Baasanjav D, Hudson LD and Goldfarb LG

    Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1361, USA.

    Spastic paraplegia type 2 (SPG2) is allelic to Pelizaeus-Merzbacher disease (PMD), with both conditions resulting from mutations in the proteolipid protein gene (PLP). We report an SPG2 family in which 3 male members and a heterozygous female member were affected with spastic paraplegia characterized by relatively late onset and mild clinical manifestations. A unique H147Y mutation in exon 3B of the PLP altering the proteolipid protein (PLP) but not the alternatively spliced DM20 isoform was identified as the cause of this distinct disease phenotype. Cellular pathology studies of SPG2 mutations offer an explanation for the paradoxical finding that mutations associated with the mildest phenotype in male family members also affect female carriers.

    Annals of neurology 1999;45;5;680-3

Literature (1)

Pubmed - other

  • Novel exon 3B proteolipid protein gene mutation causing late-onset spastic paraplegia type 2 with variable penetrance in female family members.

    Sivakumar K, Sambuughin N, Selenge B, Nagle JW, Baasanjav D, Hudson LD and Goldfarb LG

    Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1361, USA.

    Spastic paraplegia type 2 (SPG2) is allelic to Pelizaeus-Merzbacher disease (PMD), with both conditions resulting from mutations in the proteolipid protein gene (PLP). We report an SPG2 family in which 3 male members and a heterozygous female member were affected with spastic paraplegia characterized by relatively late onset and mild clinical manifestations. A unique H147Y mutation in exon 3B of the PLP altering the proteolipid protein (PLP) but not the alternatively spliced DM20 isoform was identified as the cause of this distinct disease phenotype. Cellular pathology studies of SPG2 mutations offer an explanation for the paradoxical finding that mutations associated with the mildest phenotype in male family members also affect female carriers.

    Annals of neurology 1999;45;5;680-3

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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